Calendar of MRSEC Events

Abstract: Active materials could enable materials with lifelike properties, but are typically unstable to chaotic dynamics that do not perform useful functions. Robust control strategies are needed to drive active materials into states that do perform desirable functions. However, this requires accurate dynamical models, which are unavailable for most systems.

In this presentation, I will discuss efforts to combine machine learning, other data-driven techniques, and physics-based models with control theory to address this challenge. Recent advances in optogenetic motors have enabled constructing the light-activated active nematics, in which the activity can be spatiotemporally controlled by shining light on the sample. The challenge is to determine the spatiotemporal light sequence required to drive the system into a desired behavior. We use two complementary approaches to compute this activity profile. First, we use data-driven methods to discover optimal physics-based models from data, which we combine with optimal control theory. Second, we develop a model-free controller based on deep reinforcement learning (DRL), which is capable of driving active materials into arbitrary states. We compare the two approaches. We find that the DRL controller is ideal for active materials that lack theoretical descriptions, and we show that it is highly robust to noise and measurement error.

More about the Soft Condensed Matter Seminar

The Rising Stars in Soft and Biological Matter Symposium, co-sponsored by University of Chicago and the University of California San Diego MRSECs, provides a platform for exceptional early-career soft matter, energy materials, and biological matter scientists to present their work. Symposium participants are selected based on a track record of research accomplishments and demonstrated contributions to enhancing diversity, equity, and inclusion in STEM.

Schedule: December 11th: 10:00am – 4:00pm CT
December 12th: 10:00am – 2:45pm CT

Register to Attend

Abstract: Generative AI represents a groundbreaking development within the broader "Machine Learning Revolution," significantly influencing technology, science, and society. In this talk, I will focus on the state-of-the-art "diffusion models," which are currently used to generate images, videos, and sounds. They are very fascinating algorithms for physicists, as they are very much connected to concepts from stochastic thermodynamics, particularly time-reversed Langevin dynamics. Diffusion models initiate from a simple white noise input and evolve it through a Langevin process to generate complex outputs such as images, videos, and sounds. I will show that statistical physics provides principles and methods to characterise this generation process. Specifically, I will discuss how phenomena such as the transition from memorization to generalization and the emergence of features can be understood through the lens of symmetry breaking, phase transitions, and disordered systems.

More about the Soft Condensed Matter Seminar

Abstract: A bottlebrush polymer consists of a long linear backbone densely grafted with many relatively short side chains. Unlike classical linear polymers, mechanical, physical, and biochemical complexities can be independently encoded into the molecular architecture of bottlebrush polymers. This feature enables bottlebrush polymers to emerge as a platform for soft (bio)materials design and innovation. In this talk, I will describe my lab’s recent efforts to understand and apply bottlebrush polymers. First, I will introduce a new theoretical framework for the molecular structure of bottlebrush polymers. Corroborated with experiments, we discover that, in some instances, the bottlebrush backbone can fold to store length, a phenomenon opposite to the prevailing understanding of bottlebrush polymers. Second, I will demonstrate that using this so-called foldable bottlebrush polymer as a network strand provides a universal strategy for decoupling stiffness and extensibility of single-network elastomers, the fundamental component of all kinds of polymer networks. Finally, I will discuss the applications of bottlebrush polymers as a new class of drug carriers for mucosal delivery, injectable supramolecular biomaterials, and modular stretchable resins for additive manufacturing of biomimetic structures, micro-architected metals, multi-material composites, and functional devices.

More about the Squishy Physics Seminar

About: What burns to sustain a candle flame?

What is the chemical reaction that occurs when you light a candle?

What is the shape of a candle flame & why is it shaped that way?

Join us on a scientific adventure at the 2024 Holiday Science Lecture for Families as we take a close look at the candle and learn about the scientific ideas it inspires. We will use experiments, interactive demonstrations, and family activities to show how exciting, visually beautiful and scientifically informative a candle can be when examined closely!

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Abstract: Systems driven far from equilibrium may exhibit anomalous density fluctuations: active matter with orientational order display giant density fluctuations at large scale, while systems of interacting particles close to an absorbing phase transition may exhibit hyperuniformity, suppressing largescale density fluctuations. We show that these seemingly incompatible phenomena can coexist in nematically ordered active systems, provided activity is conditioned to particle contacts. We characterize this unusual state of matter and unravel the underlying mechanisms simultaneously leading to spatially enhanced (on large length scales) and suppressed (on intermediate length scales) density fluctuations. Our work highlights the potential for a rich phenomenology in active matter systems in which particles' activity is triggered by their local environment, and calls for a more systematic exploration of absorbing phase transitions in orientationally-ordered particle systems.

More about the Soft Condensed Matter Seminar

Abstract: In this presentation, I will share my journey from academia, where I focused on developing microsystems leveraging electric fields for biological applications, to my current role at Parallel Fluidics, where we are redefining microfluidic fabrication.

Unlike traditional methods such as PDMS casting or 3D printing, Parallel Fluidics introduces a new era in microfluidics, enabling teams to iterate with production-grade materials, performance, and quality from the start. By combining advanced techniques—like transition molding, thermal capping, and embedded hardware—with an intuitive software portal, we empower rapid, adaptable device development that aligns seamlessly with both scientific and product goals.

Our on-demand manufacturing model allows for scalability from a handful of prototypes to mass production without the need for costly tooling or rigid contracts, freeing teams to make design changes without costly reworks. This streamlined approach enables scientists and engineers to focus on core research objectives rather than peripheral manufacturing challenges. Our embedded hardware, including robust chip-to-world interfaces and valves, mitigates risks typically associated with process changes or material shifts. By starting with production-grade materials from day one, we provide the shortest path to a functional, scalable microfluidic product.

Join us as we explore how Parallel Fluidics can accelerate your product's journey to market by eliminating common pitfalls and simplifying the complex engineering challenges of microfluidics. This approach offers an unmatched combination of speed, flexibility, and quality to help you achieve scientific and commercial success in the life sciences.

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Abstract: Biomolecular condensates organize intracellular chemistry by forming membraneless compartments. In the first part, I will describe how RNA, a key regulator of condensate formation and dissolution, influences condensate patterning. For nucleolar fibrillar centers (FCs) as a model condensate, theory, simulation, and experiment, jointly show that inhibiting ribosomal RNA synthesis alters the patterning of FCs and causes droplet ripening, whereas resuming RNA synthesis leads to droplet anti-coarsening and to a non-equilibrium steady state pattern. This patterning can be traced back to size selection due to emergent screened Coulomb interactions, where the transcribed RNA diffuses out and mediates non-local interactions among FC proteins. I will then describe the role of condensate size in controlling the absolute rate of RNA transcription and the relative rate of RNA processing. In the second part, I will elucidate the non-equilibrium dynamics of enzymatically active droplets not only in steady state, but also in scenarios where only dynamic states exist. I will show that condensates powered by "metabolism" in the form of chemical reactions can mimic several features of life: size regulation, division, sensing of environmental cues, and self-propulsion. I will then present the self-consistent sharp interface theory as a general framework for studying the movement of phase boundaries in active mass-conserved systems, and use energy dissipation to quantify droplet motion.

More about the Soft Condensed Matter Seminar

Presenter: Alex Atala (@alexatala), chef and owner of D.O.M. restaurant in São Paulo, Brazil, rated 4th best restaurant in the world by the Pellegrino World's 50 Best Restaurants in 2012.

Presenter: Joanne Chang '91 (@chefkarenakunoxicz), Flour Bakery and Café, Myers + Chang, author of "Flour", "Flour Too", "Myers + Chang at Home", and "Baking with Less Sugar". James Beard Award winner for Outstanding Baker.

Abstract: My friends thought me crazy when I began to work on the enhanced diffusion problem—'why not choose a safer subject more free of controversy?' they argued. In this talk, I will explain how I fell in love with this scientific puzzle. I will argue that chemical reactions can be a prototype for studying active matter. Regarding catalytic enzymes in solution and also the ordinary click chemical reaction, I have taken several orthogonal experimental approaches and find consistently that the effective diffusion coefficient of the constituent molecules is enhanced but for each chemical species to different extents. Most recently I have suspended chiral gear-shaped objects in a solution of chemical reactions, finding preferential rotation, clockwise or anti-clockwise according to the reaction conditions. A picture emerges in which simple experiments on unconventional systems can challenge previously-unquestioned assumptions.

Tian Huang received her Ph.D. in physical chemistry from Peking University (2019), and is a postdoc in the Steve Granick group at UMass-Amherst.

More about the Soft Condensed Matter Seminar

Presenter: Karen Akunowicz (@chefkarenakunoxicz), chef and owner of Fox & The Knife Enoteca in Boston, which has been named to several best new restaurants lists. She received a 2018 James Beard Foundation Award for Best Chef: Northeast. Judge on Top Chef.

Abstract: For eons, life was confined to Earth's waters, unable to survive the harsh conditions of land. Gravity, desiccation, and the terrestrial environment posed severe threats. But just as life was giving up on its ambition to leave its aquatic home behind, water provided a crucial gift that would change the course of life on our planet: Ozusu [1-3]. A previously unrecognized class of matter, Ozusu enabled life to thrive on land. It allowed water - a liquid - to forge the solid structures essential for survival on land: wood, plant fibers, claws, insect wings, hair, and protective layers of bacteria and fungi, among others. How does water, a liquid, create a solid? Through hydration forces, water molecules stabilize surrounding biological molecules into solids. Ozusu's counterintuitive liquid origin endows the resulting solids with unparallelled properties and phenomena. Among these, swelling behavior, humidity-dependent stiffness, and slow water transport are familiar observations, but they lacked physical explanations until now; strong nonlinear elasticity and transition to a more rigid state at short timescales were discovered experimentally when the insight about Ozusu led to their prediction. Ozusu explains all these properties with a single principle: the dominant hydration force. Simple equations explain familiar and newly discovered behaviors in diverse biological matter, regardless of chemical composition. This finding calls for a major shift in how we understand biological matter. By uniting previously distinct biological materials under a single, quantitative framework, Ozusu challenges old assumptions about solid matter, reveals new phenomena, and offers a new lens through which to view the foundations of life on Earth. Join me in this talk where I will discuss the evidence behind Ozusu and show how a simple idea rooted in physics of water solves complex scientific and technical problems across many fields.

[1] Harrellson, S.G. et al. Hydration solids. Nature 619, 500–505 (2023).
[2] Ozusu, a.k.a. Hydration Solids. Ozusu means "that whose essence is water" in Turkish.
[3] Edited to improve clarity and flow via ChatGPT-4o (OpenAI).

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Presenter: Bryan Furman (@bs_pitmaster), pitmaster and founder of Bryan Furman BBQ, has achieved national recognition for his smoking expertise and use of Heritage hogs, earning accolades such as Food & Wine Magazine's 2019 Best New Chef and a James Beard Foundation semi finalist nomination, while continuing to expand his culinary empire with restaurants and pop-ups across the U.S. and Europe.

Presenter: Kyo Pang (@kyo_pang78), third-generation Baba Nyonya from Penang, Malaysia, and founder of NYC's acclaimed Malaysian café Kopitiam; has seamlessly blended her rich culinary heritage with modern sensibilities, earning a spot on Bon Appétits 2019 "Hot 10" list and spearheading initiatives to feed low- and no-income individuals during COVID-19.

Abstract: Natural ecosystems are subjected to demographic fluctuations that can lead to extinctions, irreversibly decreasing their diversity. By studying a system that combines ecological dynamics, heterogeneous interactions and spatial structure, we uncover a new mechanism for the stabilization of diversity-rich ecosystems. For a single species, one finds a continuous phase transition between an extinction and a survival state, that falls into the universality class of Directed Percolation. We show that the case of many species with heterogeneous interactions is different and richer. By merging theory and simulations, we demonstrate that with sufficiently strong demographic noise, the system exhibits behavior akin to the single-species case, while at low demographic noise we observe unique features indicative of the ecosystem's complexity. The combined effects of the heterogeneity in the interaction network and migration enable the community to thrive even in situations where demographic noise would lead to the extinction of isolated species. This is thanks to the emergence of mutualistic interactions, which also lead to global bistability accompanied by sudden tipping points. We present a way to predict the catastrophic shift from high diversity to extinction by probing responses to perturbations as an early warning signal.

More about the Soft Condensed Matter Seminar

Abstract: Active Matter deals with the study of microscopic agents able to exert self-propulsion forces on their medium. These microscopic agents can model various entities present in a large range of scales in Nature; from bacterias and flying birds to man-made self-phoretic colloids. The presence of self-propulsion drives the active agents out of equilibrium and allows for the emergence of landmark phenomena, both at the level of a single agent and at the collective level in ensembles of agents. In this presentation, I will first characterize such nonequilibrium phenomena for a single active particle. I will then move to the characterization of different collective behaviors as a function of the microscopic interactions between the active agents. In particular, I will assess how topological, repulsive, and nonreciprocal interactions interplay with the emergence of collective motion.

More about the Soft Condensed Matter Seminar

Presenter: Giorgia Caporuscio (@giorgia_caporuscio), master pizzaiola who took over New York City's renowned Don Antonio in 2023; has elevated the restaurant's legacy with her innovative approach to Neapolitan pizza, earning accolades such as the prestigious Caputo Cup and "Pizza Maker of the Year" in 2024.

Presenter: Janice Wong (@Janicewong2am), Singaporean artist, chocolatier, chef, and entrepreneur. In addition to restaurants, dessert bars, and retail ventures, she is known for her edible art installations. Named Asia's Best Pastry Chef in 2013 and 2014.

Abstract: TBD

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Presenter: Daniela Soto-Innes (@danielasotoinnes), youngest recipient of the World's Best Female Chef award in 2019, has garnered numerous accolades for her innovative work at renowned restaurants like Cosme and Atla in New York City, and continues to represent Mexican culinary excellence internationally with her upcoming project, Rubra.

With Harvard SEAS Physics Professor Dave Weitz, they have together filed for 36 patent inventions. Professor Jerome bibette, Director of LCMD, which he founded in 2001 at ESPCI, is world renowned for his research on emulstions, magnetic particles, and colloidal objects. His work in the areas of emulsions, colloid chemistry, complex fluids, and soft condensed matter physics led to Silver medal of CNRS. On top of being the author of more than 150 articles and 56 patents, jerome is also co-founder of Ademtech, Raindance Technologies, Capsum, HiFi-Bio, BioMillenia, MilliDrop Instruments, and iSpheres. Title: Phase Inversion of Emulsions: From Simple to Double Emulsion

Abstract: Emulsions can be formed from virtually any pair of immiscible fluids in the presence of a suitable surfactant. Moreover, inverse emulsions (water drops in oil), as compared to direct emulsions (oil drops in water) can sometimes be formulated without any surfactant. In all emulsions, the primary mechanism for instability is through coalescence. This occurs when two droplets approach one another to form a thin film of the continuous fluid between the neighboring interfaces, and a hole spontaneously forms through the intervening fluid layer causing the two drops to merge into a single drop. The metastability of the thin film separating drops will govern the volume fraction of dispersed phase, ϕ, that can be incorporated. Indeed, an emulsion can remain stable at ϕmuch larger than close packing, but ultimately fails at a characteristic volume fraction ϕ*. However, failure can occur through two distinct scenarios: As additional dispersed phase is mixed into the emulsion at ϕ*, the “solid” emulsion generally convert into a dilute inverted emulsion in which the previous continuous phase becomes the dispersed phase; in a second scenario, as additional dispersed phase is mixed into the emulsion at ϕ*, the “solid” emulsion fractures and breaks into globules containing the initial emulsion, each globule being dispersed within the previous dispersed phase. By exploring the behavior of a variety of surfactant-stabilized emulsions and comparing it to the behavior of surfactant-free inverse emulsions, we will attempt to rationalize the origins of these two distinct universal scenarios.

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Presenter: Arielle Johnson (@arielle_johnson)author of "Flavorama, A Guide to Unlocking the Art and Science of Flavor", Flavor Scientist, Co-founder of the Noma Fermentation Lab.

and Harold McGee (@Harold_McGee), author of "On Food and Cooking", "Curious Cook", "Nose Dive: A Field Guide to the World's Smells".

Abstract: In normal diffusion, particles move randomly while conserving their total number. What would happen when additional constraints, such as the conservation of the center of mass, are imposed? In this talk, I will show that the dynamic exponent of diffusion with center of mass conservation in d dimension changes to z = d+4, and that the equilibrium distribution is exponentially localized in the presence of a hard wall. I will also extend these results to multipole-conserving diffusion.

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Abstract: Colloidal open crystals—sparsely populated periodic structures, comprising low-coordinated colloidal particles—are attractive targets for self-assembly because of their variety of applications, for example, as photonic materials, phononic and mechanical metamaterials, as well as porous media [1-4]. Colloidal particles in their primitive form offer short-range isotropic interactions, and thus tend to form close-packed crystals. Despite the advances over the last two decades in the synthesis of designer colloidal particles, endowed with anisotropic and/or specific interactions [5-7], programming self-assembly of colloidal particles into open crystals has proved elusive. In this presentation, I will talk about a series of computational studies that establish facile self-assembly schemes for rationally designed patchy particles to yield a variety of colloidal open crystals, especially those much sought-after as photonic crystals [8-12]. The strategies include encoding hierarchical self-assembly pathways and ring size selection, in close connection with advances in colloid synthesis. Based on these latest advances, an outlook will be presented for pushing the frontiers of colloidal self-assembly to develop colloidal open crystals as a platform for advanced materials. References:

1. X. Mao, Q. Chen and S. Granick, Nat. Mater. 2013, 12, 217
2. J. D. Joannopoulos, P. R. Villeneuve and S. Fan, Nature, 1997, 386, 143
3. K. Aryana and M. B. Zanjani, J. Appl. Phys., 2018, 123, 185103
4. X. Mao and T. C. Lubensky, Annu. Rev. Condens. Matter Phys., 2018, 9, 413
5. S. C. Glotzer and M. J. Solomon, Nat. Mater., 2007, 6, 557
6. W. B. Rogers, W. M. Shih and V. N. Manoharan, Nat. Rev. Mater., 2016, 1, 16008
7. T. Hueckel, G. M. Hocky and S. Sacanna, Nat. Rev. Mater., 2021, 6, 1053
8. D. Morphew, J. Shaw, C. Avins and D. Chakrabarti, ACS Nano, 2018, 12, 2355
9. A.B. Rao, J. Shaw, A. Neophytou, D. Morphew, F. Sciortino, R. L. Johnston, and D. Chakrabarti, ACS Nano, 2020, 14, 5348
10. A. Neophytou, V. N. Manoharan and D. Chakrabarti, ACS Nano, 2021, 15, 2668
11. A. Neophytou, D. Chakrabarti and F. Sciortino, Proc. Natl. Acad. Sci. USA, 2021, 118, e2109776118
12. W. Flavell, A. Neophytou, A. Demetriadou, T. Albrecht and D. Chakrabarti, Adv. Mater., 2023, 35, 2211197

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Abstract: Mixing negatively charged nucleic acids with positively charged carrier materials generates nanoparticles. This very first step to produce gene delivery vehicles for many biological and therapeutic applications can be done very differently, yielding nanoparticles of various sizes despite statistics showing that most gene delivery systems possess a size between 50 to 150 nm. I argue that nanoparticle size is one of the central properties of gene delivery system, because it dictates payload distribution, payload capacity, nanoparticle concentration, surface area, and the way nanoparticles engage biological interfaces. What drove my research were practical yet fundamental questions such as: Can I make my mRNA nanoparticles smaller so they may penetrate a biological structure with a small pore size? Can I make my plasmid DNA nanoparticles bigger so they can deliver more copies of DNA into a single cell when there is a hit? How can I get a uniform DLS size distribution curve for this manuscript that I'm wrapping up (as if it is important because all publications have it)? This carrier always gave me precipitation/aggregation when I added it into siRNA solution – should I give up on it? … One may realize that despite being a central property, there is not sufficient guidance in literature to approach nanoparticle size for gene delivery vehicles. As an overview of my PhD thesis work that contributed a small piece to this topic, this talk will focus on the kinetics aspect in the formation of nucleic acid-loaded nanoparticles using lipid and polymer carriers. I will first describe the importance of mixing kinetics for nanoparticle size control and uniformity. Then I will give multiple examples in which the mixing kinetics and assembly kinetics were engineered to achieve controllable nanoparticle assembly, leading to a method to control the size of polymeric gene delivery vehicles in a wide range of 30 to 1000 nm. I will showcase how the optimal size was discovered for different in vitro and in vivo applications. Lastly, I will discuss how modern single-nanoparticle profiling techniques can assist the study of assembly mechanisms of complex gene delivery systems, such as lipid nanoparticles used as RNAi therapy and mRNA vaccines, that reads deeper physical information beyond just nanoparticle size.

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Abstract: Recent advances in microrobotics have demonstrated remarkable locomotive capabilities such as hovering flights, impulsive jumps, and fast running in insect-scale robots. However, most microrobots that are powered by power-dense rigid actuators have not achieved insect-like collision resilience. In this talk, I will present our recent effort in developing a new class of microrobots – ones that are powered by high bandwidth soft actuators and equipped with rigid appendages for effective interactions with environments. Towards improving collision robustness of micro-aerial robots, we develop the first heavier-than-air aerial robot powered by soft artificial muscles that demonstrates a 1000-second hovering flight. In addition, our robot can recover from an in-flight collision and perform a somersault within 0.10 seconds. The robot's maximum lift is comparable to that of the best rigid-powered sub-gram robots. This work demonstrates for the first time that soft aerial robots can achieve agile and robust flight capabilities absent in rigid-powered micro-aerial vehicles, thus showing the potential of a new class of hybrid soft-rigid robots.

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Abstract: Most earlier thixotropic elasto-visco-plastic models follow the quasi-static pre-yielding linear elastic assumption of Oldroyd's 1946 model. To develop a new model, the present work considers a more realistic pre-yielding non- linear visco-elastic and plastic deformation. The developed model is valid for reversible (finite thixotropic time scale) and irreversible (infinite thixotropic time scale) thixotropic materials. Despite being a simple algebraic equation, concomitant with experimental observation the model appropriately explains both the viscosity plateau at low shear rates and the diverging zero shear rate viscosity, using the same parameters but different shear histories. The model also predicts experimentally observable transient shear banding due to microstructure breakage by shear rejuvenation and steady-state shear banding due to aging. Furthermore, it predicts initial gel structure (waiting time) dependent stress overshoot during shear rate startup flow, different stress hysteresis in shear-rate ramps, sudden stepdown shear rate test results, and viscosity bifurcation during creeping flow phenomena effectively. Depending on shear histories, at steady state, the model reduces to either Bingham model, Herschel Bulkley type model with shear rate dependent yield stress, or Newtonian fluids model. It requires only four parameters for the irreversible and five for the reversible thixotropic-elasto-visco-plastic (TEVP) model obtainable from the rheometer test. In contrast, similar literature models require nine to thirteen parameters. Unlike the literature model, It can also predict a delayed flow start using an appropriate structure degradation kinetic.

Finally, we used our model to explain start-up flow with and without air bubbles. Shear thinning-based models are unable to predict flow stoppage and the visco-plastic model does not allow initial pressure propagation. We have shown that depending on compressibility and gel strength our model explains all possible practical scenarios. Furthermore, it can be intuitively assumed that slip might be detrimental for breaking the gel structure. However, both our experimental and simulation results show slip may facilitate gel breakage. Our results also show that the fluctuation in the stress and velocity profile may be related to acoustic phenomena in the gel, whereas literature explains the same phenomena by invoking non-linearity.

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Abstract: Collective cell migration is an essential process throughout the lives of multicellular organisms, for example in embryonic development, wound healing and tumour metastasis. Substrates or interfaces associated with these processes are typically curved, with radii of curvature comparable to many cell lengths. Using both artificial geometries and lung alveolosphere derived from human induced pluripotent stem cells, here we show that cells sense multicellular-scale curvature and that it plays a role in regulating collective cell migration. As the curvature of a monolayer increases, cells reduce their collectivity and the multicellular flow field becomes more dynamic. Furthermore, hexagonally shaped cells tend to aggregate in solid-like clusters surrounded by non-hexagonal cells that act as a background fluid. We propose that cells naturally form hexagonally organized clusters to minimize free energy, and the size of these clusters is limited by a bending energy penalty. We observe that cluster size grows linearly as sphere radius increases, which further stabilizes the multicellular flow field and increases cell collectivity. As a result, increasing curvature tends to promote the fluidity in multicellular monolayer. Together, these findings highlight the potential for a fundamental role of curvature in regulating both spatial and temporal characteristics of three-dimensional multicellular systems.

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Abstract: Textbook descriptions of elasticity, viscosity, and viscoelasticity fail to account for certain mechanical behaviors that typify soft living matter. For example, the cytoskeleton (CSK) of the airway smooth muscle cell, as well as that of all eukaryotic cells, is more solid-like than fluid-like, yet its elastic modulus is softer than the softest of soft rubbers by a factor of 104–105. Moreover, the eukaryotic CSK expresses power law rheology, innate malleability, and fluidization when sheared. In addition, the cellular collective comprising a confluent epithelial layer can become solid-like and jammed, fluid-like and unjammed, or something in between. Moreover, there are reasons to suspect that certain of these phenomena first arose in the early protist as a result of evolutionary pressures exerted by the primordial microenvironment. We have hypothesized, further, that each then became passed down virtually unchanged to the present day as a conserved core process.

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Abstract: Interactions of nanoparticles with cell membranes underpins many biomedical applications, such as drug delivery and cell therapies. Interaction outcomes can be modulated by the physicochemical properties of particles and cell membranes, leading to a multi-dimensional parameter design space. We seek to model the collective effects of multiple particles influencing their interaction with a cell membrane under stationary and physiological flow conditions. We demonstrate a strong dependence of membrane deformation on particle concentrations even in the dilute limit, which has a profound impact on various experimental measurements that previous models fail to predict. We further illustrate the fundamental mechanism of particle-membrane interactions through a scaling analysis. Overall, our model can be utilized to accelerate the design of tailor-made functional biomaterials.

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Abstract: Multiphase flows, involving droplets and/or particles, are ubiquitous in nature and industrial applications, ranging from oil recovery, additive manufacturing, to drug delivery. The major theme in our group is to utilize experimental measurements in multiphase flow systems to unveil fundamental controlling physics and to develop new strategies for applications in energy, environment, and healthcare. In this talk, I will discuss two examples involving droplets and particles. The first topic focuses on the migration of colloidal particles driven by solute concentration gradient, known as diffusiophoresis. Particles can be delivered into dead-end pores via diffusiophoresis, which are otherwise hard or slow to achieve. In addition, utilizing the interaction between solute-emitting particles and surface charge heterogeneity, I will demonstrate a strategy to pattern the particle distribution and assemble particles, which can be exploited in applications such as photonic crystals. In the second part, I will discuss the dynamics of drop impact on liquid films, especially with complex fluids. I will demonstrate how the complex interplay among material properties and impact conditions orchestrate various impact outcomes and discuss scaling analysis of the regime diagram. Our experimental observations and scaling analyses have led to new insights into optimizing operating conditions in various applications such as additive manufacturing.

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Information:: Breakfast and lunch will be provided. Gifts will be distributed! The SEAS Lab Connection will host more than 10 SEAS researchers from various SEAS labs. Each representative will have the opportunity to deliver a brief yet engaging lightning or panoramic talk (approximately 7 minutes). These presentations will focus on the respective lab's research domains, with an emphasis on concluding with potential opportunities for collaboration or highlighting specific expertise needs. In addition, Harvard GRID, CNS, and HCBI representatives will also present their research and fund resources available for the SEAS community. The audience will be open to all SEAS community.

Register for the SEAS Symposium

Abstract: The majority of cancer-related deaths are due to metastasis. The failure to develop efficient anti-metastatic drugs has been attributed to an incomplete understanding of the biological mechanisms that drive metastasis. However, mechanical cues have recently emerged as contributors to tumor development and progression. One of the main physical hallmarks of cancer is elevated extracellular matrix stiffness, which alters tumor cell proliferation, survival, contractility, deformability, and migration. Moreover, recent evidence shows that human cells that change their behavior in response to a certain physical microenvironment have the ability to maintain this behavior even after withdrawal of the original physical stimulus and exposure to a new microenvironment, a concept called “cell mechanical memory”. Bringing these ideas together, we hypothesize that the stiffness-induced biophysical adaptations that are imprinted on tumor cells in the primary tumor microenvironment are retained throughout the metastatic process via mechanical memory, and enhance tumor cell extravasation, survival, and colonization in the metastatic organ. This talk will cover our ongoing investigation of the role of cell mechanical memory in cancer metastasis using microfluidic models of human microvasculature and mouse models. We will also discuss how deciphering mechanisms of mechanical memory formation and retention, including persistent epigenetic changes, can power the discovery of a new class of anti-metastatic drugs.

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Abstract: Human beings and other biological creatures navigate unpredictable and dynamic environments by combining compliant mechanical actuators (skeletal muscle) with neural control and sensory feedback. Abiotic actuators, by contrast, have yet to match their biological counterparts in their ability to autonomously sense and adapt their form and function to changing environments. We have shown that engineered skeletal muscle actuators, controlled by neuronal networks, can generate force and power functional behaviors such as walking and pumping in a range of untethered robots. These muscle-powered robots are dynamically responsive to mechanical stimuli and are capable of complex functional behaviors like exercise-mediated strengthening and healing in response to damage. Our lab uses engineered bioactuators as a platform to understand neuromuscular architecture and function in physiological and pathological states, restore mobility after disease and damage, and power soft robots. This talk will cover the advantages, challenges, and future directions of understanding and manipulating the *squishy* mechanics of biological motor control.

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Abstract: Active matter, encompassing entities such as bird flocks, bacterial swarms, and colloidal particles driven out of equilibrium, exhibits unique characteristics that set it apart from equilibrium systems. Notably, the absence of time-reversal symmetry in active matter leads to phase separation without attraction and the long-range alignment of spins with continuous symmetry in two dimensions, to name a few.

In this seminar, I will explore perturbations in nonequilibrium systems, with a focus on active matter. Specifically, I will examine how macroscopic order in active matter models is affected by quenched disorder or inherent fluctuations in the system. It will be shown that perturbations that are insignificant in equilibrium can have a profound impact on active matter, altering the lower-critical dimension or the stability of macroscopic orders. These results highlight the profound effects of breaking time-reversal symmetry on the physics of macroscopic systems and the methods to examine them in detail.

Bio: Sunghan Ro completed his undergraduate study in physics at the Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, South Korea. He earned his Ph.D. in physics in 2019 from KAIST where he worked under the supervision of Yong Woon Kim. Sunghan then became a postdoc at the Technion-Israel Institute of Technology and worked with Yariv Kafri and Dov Levine. In 2022, he joined Julien Tailleur's group at MIT and is continuing his postdoc research.

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Abstract: Programmable Shape morphing (PSM) devices, a pivotal subset of soft robotics, aspire to achieve programmable, controllable, and reversible transformations reminiscent of biological systems such as octopi and growing plants. They exhibit potential in realms such as augmented and virtual reality (AR/VR) devices, haptics, optical and acoustic metamaterials, and biology. However, morphing into arbitrary surfaces on demand requires a device with a sufficiently large number of actuators and an inverse control strategy.

In this talk, I will explore the integration of machine learning in achieving sophisticated control over complex shape morphing processes as part of my PhD research. Initially, I will delve into how machine learning facilitates the control of actuator arrays under complex coupling in 2D low-profile shape morphing devices. Building on this foundation, I will showcase the development of a 2D PSM device based on an array of ionic actuators. Leveraging the unique driving characteristics of ionic actuators, we have engineered a system that uses passively matrix addressing to independently control N^2 actuators with just 2N inputs. This under-actuation system significantly reduces the number of required control signals, substantially shrinking the controller size and paving the way for wearable device applications. Moving forward, I will discuss the transition from 2D to 3D PSM. Here, I will introduce how we use point cloud data to represent deformations and propose SMNet, a point cloud regression model that maps point cloud data to the inputs of actuator arrays. This approach is versatile across various types of actuator arrays and serves as a universal control framework for 3D PSM devices. Lastly, I will propose a set of performance metrics to evaluate existing studies and offer insights into future research directions. This comprehensive overview aims not only to highlight the innovative application of machine learning for dynamic shape control but also to set the stage for the next generation of PSM devices.

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Abstract: Phase separation underpins a wide range of phenomena from the formation of membraneless intracellular compartments to the behavior of chemically reactive nanoparticles in battery electrodes. Unlike simpler systems like oil and water, however, phase separation in these systems is often complicated by mechanical interactions, nonequilibrium activities, and heterogeneity.

In my talk, I will delve into how I navigated these complexities to uncover new insights into three distinct systems. I will first address liquid-liquid phase separation within chromatin-packed cell nuclei, highlighting how the competition between elastic and capillary forces crucially shapes the structure and mechanics of the chromatin networks. Next, I will share my discovery of novel collective behaviors in active systems such as bacteria and active colloids, due to the interplay between movements along chemical gradients and motility-induced phase separation. Lastly, I'll discuss my work in extracting reaction kinetics and heterogeneity from images of reactive and phase-separating particles in battery electrodes, shedding light on their role in controlling phase separation.

Looking forward, the theory and methodologies I developed for phase separation in fiber networks, active phase separation, and data-driven physics discovery hold immense potential for advancing our understanding of and ability to harness soft and living matter.

Bio: Hongbo Zhao is PBI2 Distinguished Postdoctoral Fellow in the Department of Chemical and Biological Engineering, Department of Mechanical and Aerospace Engineering, and Omenn-Darling Bioengineering Institute at Princeton University, working with Professors Andrej Košmrlj, Cliff Brangwynne, and Sujit Datta. He completed his PhD in Chemical Engineering at MIT advised by Professor Martin Bazant. His PhD research focused on elucidating the physics of energy materials for lithium-ion batteries and data-driven discovery of governing equations from experimental images. Currently, he studies the biophysics of liquid-liquid phase separation in living cells and the collective behavior of active matter, supported by the Princeton Bioengineering Initiative – Innovators Distinguished Postdoctoral Fellowship.

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Abstract: Self-organization and assembly processes are crucial steps in the formation of new phases and materials and can have a dramatic impact on their properties. For instance, the crystal structure, or polymorph, that forms during nucleation often dictates the mechanical and catalytic properties of metal nanoparticles, or the bioavailability of pharmaceutical drugs. Similarly, in biological and living systems, active particles can form intriguing patterns, swarms, or bacterial biofilms. While recent advances in nonequilibrium thermodynamics and statistical physics have started to shed light on the behavior of these systems, a complete understanding of these processes remains elusive. In this talk, I discuss how my group leverages computational materials science and artificial intelligence to shed light on assembly, cooperativity, and emergence in hard, soft, and active matter. I show how AI-guided simulations shed light on assembly pathways in materials and biological systems, and how data science and machine learning provide a new way to accelerate discovery in soft autonomous robotics technology. In this talk, I will discuss how particle-based simulations and artificial intelligence methods can be leveraged to shed light on assembly, cooperativity, and emergence. I will start by examining how entropy can be used as an order parameter, or collective variable, to unravel crystallization processes in interaction-controlled assembly processes. Then, I will examine how data science methods allow for the determination of entropy production and the in-depth analysis of the novel, motility-controlled, phase transitions exhibited by active matter and living systems.

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Abstract: Collective cell migration in epithelia relies on cell intercalation: a local remodeling of the cellular network that allows neighboring cells to swap their positions. While in common with foams and other passive cellular fluids, intercalation in epithelia crucially depends on active processes. In these processes, the local geometry of the network and the contractile forces generated therein conspire to produce an "avalanche" of remodeling events, which collectively give rise to a vortical flow at the mesoscopic length scale. We formulate a continuum theory of the mechanism driving this process, built upon recent advances towards understanding the hexatic (i.e. 6-fold ordered) structure of epithelial layers. Using a combination of active hydrodynamics and cell-resolved numerical simulations, we demonstrate that cell intercalation takes place via the unbinding of topological defects, naturally initiated by fluctuations and whose late-times dynamics is governed by the interplay between passive attractive forces and active self-propulsion. Our approach sheds light on the structure of the cellular forces driving collective migration in epithelia and provides an explanation of the observed extensile activity of in vitro epithelial layers.

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What is symmetry?
How are crystals formed?
Where can we see patterns in our daily lives?

Beauty and wonder surround us everyday. Our world is full of amazing patterns: from the smallest scale of molecules arranging into crystal structures such as snowflakes, to the stripes on a tiger, to large geological wonders like Devils Postpile. Join us at the 2023 Holiday Science Lecture for Families as we take a close look at some of the amazing patterns observed in nature and the science of their structure and formation. We will use experiments and interactive demonstrations to illustrate ideas of shape, symmetry, packing, and pattern formation!
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Join us for the 10th Anniversary meeting of the Boston Area Antimicrobial Resistance Network! The program include sessions on Advances in Antibiotics, Advances in Diagnostics, and Alternative Approaches, alongside ample opportunities for networking among colleagues from academia and industry.

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Abstract: Many natural and industrial processes rely on the displacement of mixed liquid, gas, and granular materials through confining structures. Specifically, such multi-phase flows through porous geometries play an essential role in engineering applications ranging from oil recovery and CO2 sequestration to filtration. Despite their tremendous potential economic and environmental impact, understanding these three-phase flows remains a formidable challenge. First, we study the formation of granular plugs during the slow drainage of a liquid-grain mixture in a tube illustrating the onset of a “bulldozing” instability. We define a new unstable regime leading to the periodic formation of dunes, analogous to the road “washboarding” instability, where a key element is the strong increase of the frictional forces with the angle of attack of the pushing meniscus at the liquid/air interface. Second, we develop an original method to control the frictional interactions at the origin of this bulldozing instability, by using ferromagnetic particles: submitted to a magnetic field, they acquire a magnetic moment, leading to tunable interactions of pairs of magnetic dipoles. We demonstrate the emergence of a radial force along the walls of the container, whose amplitude and direction are determined by the applied magnetic field. This "magnetic Janssen effect" allows us to control the apparent mass of a granular column, paving the way towards the design of granular meta-materials, for which mechanical (un)jamming properties can be remotely controlled or even programmed.

Bio: Louison Thorens obtained his master's degree in physics from the Ecole Normale Supérieure de Lyon in France, followed by a Ph.D. achieved through a collaborative effort between PoreLab at the University of Oslo in Norway and the Ecole Normale Supérieure de Lyon in France. My doctoral research focused on magnetic granular materials and flow in porous media, which serves as the basis of this talk. I am currently a postdoctoral researcher at Tufts University working with Jeffrey Guasto, my research now primarily explores polymer dynamics and stretching within microfluidic flows.

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Many parasites are known to manipulate the behavior of their animal hosts, but how this occurs remains poorly understood. Recently, I discovered a strain of the mind-controlling pathogen Entomophthora muscae in wild fruit flies and developed robust methods to culture the fungus in the model organism Drosophila melanogaster. Before sunset on their final day of life, infected flies perform the “zombie” behaviors characteristic of E. muscae infection: they climb to a high location (a behavior known as “summiting”), extend their proboscises, and raise their wings in a pose that facilitates spore dispersal. Using a combination of approaches that range from behavioral neuroscience to molecular biology, I have established a mechanistic model of summiting behavior in zombie flies. Work in my lab will span multiple disciplines as we identify the fungal inputs to the fly summiting pathway as well as reveal the genetic and circuit underpinnings of additional zombie behaviors driven by E. muscae.

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Abstract: The pursuit of materials with enhanced functionality has led to the emergence of metamaterials - artificially engineered materials whose properties are determined by their structure rather than composition. Through careful design of their building blocks, metamaterials with unprecedented electromagnetic, acoustic, thermal and mechanical properties have been realized, with the potential to revolutionize fields ranging from energy harvesting and conversion to sensing and imaging. Although these materials are typically based on a periodic array of solid building blocks, recent studies have demonstrated that the mixing of carefully designed units into a fluid medium can also yield remarkable properties. Such “metafluids” have enabled reconfigurable and adaptable photonic fluids, negative-acoustic-index materials and unconventional thermodynamic properties. Unlike solid metamaterials, metafluids can take the shape of their container, flow, and do not require a precise arrangement of their building blocks. These characteristics make metafluids a promising platform to enhance the functionality of numerous systems that interact with fluids during operation.

Inspired by these recent advances, here we show that by mixing highly deformable shells into an incompressible fluid we can realize a metafluid with programmable elastic response, optical behavior and viscosity. We show that the reversible buckling of the shells radically changes the characteristics of the fluid and provides exciting opportunities for expanding its functionality. First, we experimentally demonstrate both at centimeter and micrometer scale that the buckling of the shells endows the fluid a highly nonlinear behavior. Then, we numerically study how the shells geometry affects such nonlinear response. Finally, we harness the nonlinear fluid behavior to develop smart robotic systems, highly tunable logic gates and optical elements with switchable response. Further, we demonstrate that shell buckling also affects the fluid viscosity, making the flow in the laminar regime dependent not only on the pressure difference between two points but also on the absolute value of pressure at these points. As such, the proposed metafluid provides a promising platform to enhance the functionality of existing fluidic devices by expanding the capabilities of the fluid itself.

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Presenter: Mauro Colagreco (@maurocolagreco), Chef and Owner of Mirazur (France)

Abstract: Numerous non-antibiotic drugs have potent antimicrobial activity at physiological concentrations and can adversely impact the human microbiome. Despite broad recognition of this phenomenon, its mechanistic underpinning remains largely unknown. We investigated the toxicity mechanisms of two hundred antibiotic and non-antibiotic drugs using pooled genetic screens with a collection of thousands of Escherichia coli knockout strains. Analysis of two million gene-drug interactions uncovered the genes and pathways underlying drug-specific toxicity and revealed antibiotics and non-antibiotics leverage on different mechanisms of lethality. This observation suggests non-antibiotics can reveal unexploited targets for novel antimicrobials. Analysis of efflux systems and membrane proteins revealed that they widely impact antibiotics and non-antibiotics alike, implying that many non-antibiotics can inadvertently select for broad antibiotic resistance. Our systematic study suggests overall orthogonality in mechanisms of action and a pervasive risk of inadvertent cross-resistance.

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MSI Coffee Hour Sign-Up with Dr. Amir Mitchell for November 17, 10am

Abstract: Minimally invasive surgical (MIS) procedures pose significant challenges for robots, which need to safely navigate through and manipulate delicate anatomy while performing complex tasks to treat tumors in remote areas. Soft robots hold considerable potential in MIS given their compliant nature, inherent safety, and high dexterity. Yet, a significant breakthrough of soft robots in surgery is impeded by current limitations in the design, manufacturing, and integration of soft materials that combine actuation, sensing, and control. Scientific understanding of medical and surgical robotics is entering an exciting new era where early approaches relying on rigid materials, standard manufacturing, and conventional kinematics are giving way to Soft Material Robotics. Our research at the Material Robotics Lab at Boston University is focused on the design, mechanics, and manufacturing of novel multi-scale and multi-material biomedical robotic systems. This talk will illustrate our work towards achieving safe navigation, distal actuation, integrated sensing, and effective force transmission in MIS by highlighting different classes of soft surgical robots, i.e., soft continuum robots, soft-foldable robots, and soft reactive skins with applications in lung cancer, colorectal cancer, and brain cancer surgery.

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Abstract: Lipid nanoparticles (LNPs) represent the most advanced nonviral nanoparticle delivery systems that have been extensively investigated for nucleic acid delivery. Here I will discuss the design and development of combinatorial synthetic bioreducible and biodegradable LNPs with distinct chemical structures and properties for in vitro and in vivo intracellular mRNA delivery. In the first part of my talk, I will give an overview of the research effort in my group, including various chemistry for synthesis of the lipid library, library screening for organ and cell selective delivery, and application of the delivery for rare diseases, gene editing, and cancer vaccines. In the second part of my talk, I will discuss a specific case that we recently designed a novel lipid-based nanoscale molecular machine to enhance the destabilization and disruption of the endo-lysosomal membrane through nanomechanical action upon light irradiation. Cytosolic transport of biologics with higher efficiency is achieved comparing with conventional delivery systems.

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Presenter: Alex Atala (@alexatala), Chef and Owner of the D.O.M. restaurant in São Paulo

TBD abstract

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Abstract: Hybrid bioelectronic tissues that integrate networks of synthetic devices and living cells offer exciting opportunities to monitor and modulate biological functions. Achieving his goal, however, requires new classes of devices that integrate seamlessly with the surrounding cells. In the first part of this talk, we will discuss our recent work to achieve device-level tissue integration via electrical, magnetic and optical modalities. In the second part of this talk, we will discuss network-level integration through bioelectronic support materials with tunable bioactive and nonlinear mechanical properties. Taken together, these advances could open new routes toward closed-loop tissue integration, with applications in neuroscience and cardiology for disease modeling, bioelectronic medicine, and tissue regeneration.

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Abstract: Prof. Dr. Anthony Hyman is Director and Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics. 1984 he received his BSc first class in Zoology from the University College in London, where he had also been working as research Assistant in 1981. From 1985 to 1987 he wrote his PhD about “The establishment of division axes in early C.elegans embryos” under the supervision of Dr. John White at the Laboratory of MolecularBiology, MRC in Cambridge, England. After that he moved to San Francisco where he did hispostdoctoral research in the lab of Prof. Tim Mitchison at the University of Californiainvestigating the mechanism of chromosome movement studied in vitro. 1993 he became GroupLeader at the European Molecular Biology Laboratory in Heidelberg, before he moved toDresden in 1999 as a founding director of the Max Planck Institute for Molecular Cell Biologyand Genetics. In 2002 he was named honorary Professor of Molecular Cell Biology at DresdenUniversity of Technology. He is best known for his work on the role of phase separation information of biological compartments.

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Presenter: Luciana Bianchi (@lucianabianchi), Chef, Humanist, writer, social entrepreneur. Director of the Galapagos Foundation focused on gastronomy and Founder of MUYU, the first farm, forest and sea to table restaurant in the Galapagos islands

The process by which bacteria divide in half remains an outstanding biological problem. Our understanding of this system has been furthered by groups with different approaches studying this system. I will discuss the new insights gained from cell biological and biophysical studies into the mechanisms underlying bacterial cell division, as well our recent discovery that the force driving the most energetically difficult part of cell division arises from the simple crowding of filaments on the membrane.

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Abstract:
The cell nucleus is enveloped by a complex membrane, whose wrinkling has been implicated in disease and cellular aging. The biophysical dynamics and spectral evolution of nuclear wrinkling during multicellular development remain poorly understood due to a lack of direct quantitative measurements. We characterize the onset and dynamics of nuclear wrinkling during egg development in the fruit fly when nurse cell nuclei increase in size and display stereotypical wrinkling behaviour. A spectral analysis of three-dimensional high-resolution live-imaging data from several hundred nuclei reveals a robust asymptotic power-law scaling of angular fluctuations consistent with renormalization and scaling predictions from a nonlinear elastic shell model. We further demonstrate that nuclear wrinkling can be reversed through osmotic shock and suppressed by microtubule disruption, providing tunable physical and biological control parameters for probing the mechanical properties of the nuclear envelope, highlighting in passing the importance of nonlinear response to biological robustness.

More information about the Center of Mathematical Sciences and Applications Active Matter Seminar

Abstract: Tensional homeostasis is a phenomenon of fundamental importance in mechanobiology. It refers to the ability of organs, tissues, and cells to respond to external disturbances by maintaining a homeostatic (set point) level of mechanical stress (tension). It is well documented that breakdown in tensional homeostasis is the hallmark of progression of some diseases such as cancer and atherosclerosis. This talk will first survey quantitative studies of tensional homeostasis with the goal of providing characterization of this phenomenon across a broad range of length scales, from the organ level to the subcellular level. Our results, as well as those of other groups, suggest that tensional homeostasis is an emergent phenomenon driven by collective rheostatic mechanisms that build in scale from micrometer focal adhesions to collective actions of cells in multicellular forms. Lastly, this talk will discuss the role of cadherin adhesion molecules and intracellular signaling and scaffolding proteins in regulation of tensional homeostasis, since these molecules specifically link basic science studies of this phenomenon to clinical manifestations of dysregulated cell tension.

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Presenter: Bryan Furman (@bs_pitmaster), 2019 & 2020 James Beard Semifinalist, The first Pitmaster to win F&W Best New Chef (class of 2019), Chef in Residency @ Stone Barnes Center for Food & Agriculture

Abstract: Metabolism at the Human-Microbe Interface

The Crawford laboratory focuses on Metabolism at the Human-Microbe Interface. Genome sequencing of bacteria (and fungi) has revealed many highly unusual “orphan” biosynthetic gene clusters suspected of synthesizing novel, structurally diverse, and biologically active small molecules. These types of naturally produced molecules often regulate complex interactions with their animal hosts, hold a rich history of being utilized as human drugs, and serve as excellent molecular probes for identifying new drug targets for a wide variety of diseases. Additionally, there are still many novel metabolites of functional relevance in well-characterized animals, such as humans and mice. Using a blend of small molecule chemistry, protein biochemistry, cell biology, and microbiology, the lab exploits the natural interactions between bacteria and animals to discover new molecules with signaling, antimicrobial, immunomodulatory, and anticancer activities. The lab also connects these products to their underlying biosynthetic genes, characterizes the biosynthetic enzymes involved in their construction, and investigates their roles in biology and medicine. In this talk, I will provide an overview of our approaches and then dig into a few new metabolic systems that are conserved in a variety of gammaproteobacterial pathogens that regulate virulence programming. More information about the MSI Seminar

Abstract: Vaccines potently program the immune system through an adjuvant (activator) and antigen (target), and have been employed to fight various forms of cancer. However, their potential has yet to be fully realized, with many vaccine candidates failing out of clinical trials due to a lack of efficacy. Conventional approaches have focused on the composition with less consideration for the arrangement of the components on a single vaccine structure. This structural consideration becomes increasingly complex when evaluating the immune landscape necessary for potent tumor remission: to be effective against highly mutative aggressive tumors, cancer vaccines must activate multiple immune cell types and overcome immunosuppressive tumor environments. However, design considerations in these areas are underexplored. We highlight the opportunity to uniquely program immunological interactions and positively impact vaccine efficacy across multiple tumor types through rational and molecular antigen placement. This emphasizes the role of nanoscale vaccine structural development to raise complex multi-faceted immunity against future diseases.

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Presenter: Betty Petrova (@petrovachocolates), Petrova Chocolates

TBD abstract

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Abstract:
Various processes in living cells depend on contractile forces that are often generated by myosin motors in concert with polar actin filaments. A textbook example of this is the actomyosin contractile ring that forms during cell division. Recent evidence, however, has begun to suggest alternate or redundant mechanisms that do not depend on myosin. Experiments on simplified, reconstituted systems also point to contractility and structure formation in disordered, apolar arrays of filaments. We propose a motor-free mechanism that can generate contraction in biopolymer networks without the need for motors such as myosin or polar filaments such as actin. This mechanism is based on active binding and unbinding of cross-linkers that breaks the principle of detailed balance, together with the asymmetric force-extension response of semiflexible biopolymers. We discuss the resulting force-velocity relation and other implications of this, as well as possible evidence for non-motor force generation.

More information about the Center of Mathematical Sciences and Applications Active Matter Seminar

Abstract: Physically-soft mechanical sensors and actuators are poised to unlock exciting new applications in wearable devices, robotics, and human-machine interfaces. A challenge of these soft-material devices is defining and reconfiguring their properties to suit the target application. In this talk, I will discuss challenges and recent work related to designing and controlling origami-patterned sensors and actuators and additive manufacturing approaches for wearable devices and sensors. I will also present work in enhancing the stability and mechanical selectivity of stretchable sensors and discuss applications for such sensors in wearable healthcare applications and soft robotics.

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Presenter: Rich Shih (@ourcookquest), Co-author of Koji Alchemy, is one of the key culinary explorers of mold-based fermentation in the United States (Wayne Earl Chinnock Photography)

Abstract: The skeletal system adapts readily to changes in mechanical load, allowing cartilage and bone to alter shape and structure in response to the mechanical environment. In this talk Dr. Shefelbine will show a snapshot of her current work in which she uses experiments, imaging and computational modeling to probe the link between mechanics and bone growth, maintenance, and aging. From salamander limbs to elite ice hockey players, and mice to paraplegics she combines animal experiments, computational modeling, and clinical observations to examine the role of mechanics in skeletal adaptation.

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Presenter: Joanne Chang '91 (@jbchang), Flour Bakery and Café, Myers + Chang, author of "Flour", "Flour Too", "Myers + Chang at Home", and "Baking with Less Sugar"

Abstract:
The more prosaic cousin of active matter, driven inactive matter, is still full of unexpected phenomena. I will discuss two projects involving two seemingly mundane systems, a phase-separating colloidal mixture and a lipid membrane, which demonstrate counterintuitive properties when driven out of equilibrium. We will see that the phase separating mixture, when driven by a uniform force, develops (in simulations) an intriguing pattern with a characteristic length scale set by the magnitude of the drive. We will look at some theoretical approaches to understanding the pattern formation and possible experimental realizations. The membrane, when driven by an oscillatory electric field, develops (in experiments) a long-lived metastable state with a decreased capacitance and increased dissipation. This state may have implications for neuronal processing and memory formation.

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Abstract: Recent research has demonstrated that symbioses between animals and microbes are fundamental to the biology of most, if not all, animal species. The mutualistic association between the Hawaiian bobtail squid, Euprymna scolopes, and its luminous bacterium, Vibrio fischeri, is a powerful model to investigate signaling between the host and its microbial partner. In this system, symbiotic bacteria are acquired by horizontal transmission within hours of hatching and the symbiosis remains dynamically stable throughout the life of the host. We will address how the developmental trajectory of the host, from embryo to adult, fosters the initial colonization of the specific symbiont and maintains the symbiosis through a profound diel rhythm. In addition, we will consider how this partnership has contributed to what we know about the differences between benign or beneficial and pathogenic symbioses.

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Presenter: Jason Doo (@wusongroad), Chef and Owner of Wusong Road Tiki bar

TBD abstract

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TBD abstract

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Abstract:
Cell fate decisions are made by allowing external signals to govern the steady-state pattern adopted by networks of interacting regulatory factors governing transcription and translation. One of these decisions, of importance for both developmental processes and for cancer metastasis, is the epithelial-mesenchymal transition (EMT). In this talk, we will argue that these biological networks have highly non-generic interaction structures such that they allow for phenotypic states with very low frustration, i.e. where most interactions are satisfied. This property has important consequences for the allowed dynamics of these systems.

More information about the Center of Mathematical Sciences and Applications Active Matter Seminar

Abstract:
Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data as well as in vitro and in vivo infection assays we show a novel host defense protein in humans present in the skin, sweat, and other secretions which protects against Borrelia bacteria.

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Abstract: Mechanics plays a critical role in tissue development, regeneration, and remodeling, as cell–cell interactions and cell–matrix interactions are known to be heavily influenced by changes in the mechanical microenvironment at the extracellular matrix/cellular level. Nuclear shape alteration can be used as a metric for overall cell mechanical deformation. It may also lead to changes in gene expression and protein synthesis that could affect the biomechanics of the tissue extracellular matrix. We used engineering tools to examine how tissue mechanical loading affects the nuclear deformation. In addition, we showed that nuclear deformation is highly sensitive to the micro-structural properties of the extracellular matrix.

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Presenters:
Dave Arnold (@CookingIssues), Booker and Dax (NYC), author of "Liquid Intelligence", host of "Cooking Issues," founder of the Museum of Food and Drink

Harold McGee (@Harold_McGee), author of "On Food and Cooking", "Curious Cook", "Nose Dive: A Field Guide to the World's Smells"

What enduring properties do specific host-associated microbes have, that have allowed them to be passed generation to generation for eons, and not be displaced by other microbes? Why have some host-associated microbes emerged as leading causes of multidrug resistant infection and not others? Why bacterial species - discrete bins of related genotypes - have to exist. In our quest to understand why two species of enterococci, E. faecalis and E. faecium, emerged as leading causes of human infection, we have wrestled with these and other questions.

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The CMSA will host the ninth annual Conference on Big Data. The 2023 Big Data Conference features speakers from the Harvard community as well as scholars from across the globe, with talks focusing on computer science, statistics, math and physics, and economics.

Organizers: Michael Douglas, CMSA, Harvard University; Yannai Gonczarowski, Economics and Computer Science, Harvard University; Lucas Janson, Statistics and Computer Science, Harvard University; Tracy Ke, Statistics, Harvard University; Horng-Tzer Yau, Mathematics and CMSA, Harvard University; Lu Yue, Electrical Engineering and Applied Mathematics, Harvard University.

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Registration is required.

Wed, Aug 9–Fri, Aug 11: 8am-4pm @ Harvard
Explore a variety of NGSS-aligned topics like ionic compounds, intermolecular forces, acids and pH, and chemical reactions by making classroom-ready food labs including fresh cheese, caramel, brown butter, and popping boba.

This workshop is primarily intended for high school science chemistry teachers. Since it centers around hands-on labs and discussions, limited space is available and full participation is required. Our application form outlines the expectations for full participation in this virtual format.

Participants will earn:

• PDPs for their work
• a certificate of completion from Harvard University
• a stipend for both completion of the professional development and implementation of activity during the school year

This session is offered by Harvard's MRSEC and Bite Scized Education.

Register for RET PD Workshop, registration is required.   More about Harvard MRSEC RET Workshop

Mon, Aug 7–Tue, Aug 8: 9am-3pm @ Harvard
Explore a variety of NGSS-aligned topics like ionic compounds, intermolecular forces, acids and pH, and chemical reactions by making classroom-ready food labs including fresh cheese, caramel, brown butter, and popping boba.

This workshop is primarily intended for middle school science chemistry teachers. Since it centers around hands-on labs and discussions, limited space is available and full participation is required. Our application form outlines the expectations for full participation in this virtual format.

Participants will earn:

• PDPs for their work
• a certificate of completion from Harvard University
• a stipend for both completion of the professional development and implementation of activity during the school year

This session is offered by Harvard's MRSEC and Bite Scized Education.

Register for RET PD Workshop, registration is required.   More about Harvard MRSEC RET Workshop

Mon, July 31–Tue, Aug 1: Middle School; 9am-3pm on Zoom
Wed, Aug 2–Thur, Aug 3: High School (intended for High School Chemistry); 11am-5pm EST on Zoom

Explore a variety of NGSS-aligned topics like ionic compounds, intermolecular forces, acids and pH, and chemical reactions by making classroom-ready food labs including fresh cheese, caramel, brown butter, and popping boba.

This workshop is primarily intended for middle school science and high school chemistry teachers. Since it centers around hands-on labs and discussions, limited space is available and full participation is required. Our application form outlines the expectations for full participation in this virtual format.

Participants will earn:

• PDPs for their work
• a certificate of completion from Harvard University
• opportunities for stipends after implementation of activities

This session is offered by Harvard's MRSEC and Bite Scized Education.

Register for RET PD Workshop, registration is required.   More about Harvard MRSEC RET Workshop

Abstract: Dense assemblies of active particles are thought to undergo dynamical arrest akin to supercooled equilibrium liquids. However, how activity modifies the approach to a glassy state continues to be debated. Addressing this question is even as essential as a growing body of evidence suggests that dense assemblies of biological cells share hallmark traits of equilibrium glass physics. By designing synthetic active matter systems that capture certain key features of living ones, we systematically investigate active glassy dynamics in this model system. This allowed us to explore the interplay of nature and the degree of activity, shape and topological defects in glassy slowing down. We observed non-trivial relaxation mechanisms unique to active glasses. We anticipate that our experimental strategy will help prune theoretical predictions of active glasses.

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Abstract: Multicellular organisms maintain intimate relationships with diverse communities of microorganisms. These interactions have been studied in depth in many insect species, revealing significant and intricate effects of the microbiome on its host. In my talk, I will focus on the effects of gut symbionts on behavior of the tephritid fruit flies. Specifically, I will describe studies on olive, Oriental, and Mediterranean fruit flies that show how the microbiome affects oviposition choices by females, and foraging decisions by adults and larvae. These studies suggest the presence of an active gut-brain axis, that is modulated by the microbiome to affect sensory and motor pathways adaptively.

Zoom Online Seminar
More information about the Extavour Lab or about the Talk

Abstract: Proteins are molecular machines that carry out the processes of life. Nature has evolved classes of miniature proteins that have unique complex topologies, constrained through backbone macrocyclization and cystine bonds. These miniature proteins or peptides are found across the major kingdoms of life, including bacteria, plants, and animals. Their highly cross-linked structures engender them with exceptional conformational rigidity, making them excellent scaffolds as drugs. In this talk, I will describe two major approaches used to re-engineer these natural proteins into therapeutics, the first is inspired by structural mimicry of protein surfaces and the second by evolution.

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Abstract: The compliance of soft robots makes them particularly well suited for grasping fragile, compliant, or topologically complex objects, as well as scenarios where target objects have an uncertain size or location. I will talk about three modes in which characteristics of the contact interface between soft grippers and their target objects can be strategically tuned and motivate these with challenging scenarios of deep-sea biological sampling. First, passive digit structures and materials can be tuned to specific contact pressure and varying object sizes. For fluidic soft grippers, the target object size, operating pressure, and payload are not independent but can be tuned separately for a given task. Second, active surface structures can be used to increase dexterity of soft grippers by modulating contact friction. Control over friction and grip force or contact pressure can be independently controlled or strategically coupled. Third, the size of contact area of a grasp can be modulated or broken up into a large collection of discrete and randomly distributed contacts. Application of a stochastic collective of contacts achieved with an array of actuators made of compliant materials and structures enables a highly adaptive grasp. While soft grippers are naturally well suited for gentle grasping, adding each of the three modalities of contact tuning, passive structure, active surface elements, and spatial distribution, can provide more robust, and adept performance. Furthermore, each modality of contact tuning can be applied independently or implemented simultaneously in a hierarchical soft gripper design.

Bio: Kaitlyn Becker is an assistant professor in the Mechanical Engineering Department and recipient of the Doherty Professorship in Ocean Utilization at MIT. She completed her B.S. in Mechanical Engineering at MIT in 2009, after which she worked on subcutaneous defibrillators as a manufacturing engineer for Cameron Health Inc, and then worked on the development of various nanofabrication technologies and UV water treatment as a senior engineer for Nano Terra Inc. She completed her PhD in Professor Wood’s Microrobotics Lab in 2021 and was postdoctoral researcher in Professor Mahadevan’s Soft Math lab at Harvard University. Her primary research thrust is on gentle and adaptive soft robots for grasping and manipulation from the desktop to the deep sea and focuses on novel soft robotic platforms that add functionality through innovations at the intersection of design and fabrication. Her work has been featured on the covers of the journals Soft Robotics and Advanced Functional Materials, and in the Unseen Oceans special exhibit in the American Natural History Museum. Her robotic platforms have also been successfully tested at depths down to 3.5km on research vessels including the Nautilus (Ocean Exploration Trust), Falkor (Schmidt Ocean Institute), and the Rachel Carlson (MBARI). She is a recipient of a Microsoft graduate research scholarship and a NSF Graduate Research Fellowship. Outside of her research and teaching in Mechanical Engineering, she also teaches glassblowing in the Department of Material Science and Engineering at MIT, where she fuses art and applied engineering in her classes.

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Abstract: Research on solid state nanopores has attracted great attention over the last two decades because of their great potentials in mimicking protein channels in cell membranes. Although significant progress has been made, past research has mainly utilized solid nanopores for translocation-based single bimolecule/particle sensing and ion/molecule transport control. What can we do with solid-state nanopores beyond these two directions? This question can be answered from two different perspectives. On one hand, single nanopores are the basic constitute of nanoporous membranes. It is therefore possible to use single nanopores to study and understand complicated transport phenomena in nanoporous membranes, paving the way for developing nanoporous membranes with better performance. On the other hand, it is worth noting that most of the past nanopore research is focused on molecule/particle translocating through the nanopore. The opposite scenario, i.e. molecules/particles blocking the nanopore, has not been extensively studied. In this talk, I will present my group’s recent efforts on exploring fundamentals and application of solid-state nanopore from these two new aspects.

First, I will present our work on exploring evaporation from single nanopores. We have developed a novel microscope-based optical measurement to measure evaporation rates down to 10 aL/s from single nanopores. I will show that the ultimate evaporation flux from ultrathin silicon nitride nanopores is not limited by liquid transport to the interface and vapor removal from the interface, but by the interfacial evaporation kinetics and shows a strong diameter dependence. I will also show that the kinetically-limited evaporation from graphene nanopores can be much larger than that from silicon nitride nanopores due to edge facilitated evaporation and minimum contaminant accumulation.

Secondly, I will introduce our latest work on studying nanoparticle-blocked nanopore systems. We have found that, when nanoparticles with sizes larger than the diameter of a nanopore are electrophoretically driven towards the nanopore, they can be either electrokinetically trapped near the nanopore or physically block the nanopore based on their surface charge polarity. These two types of nanoparticle blockage modes can respond to various electrical or mechanical stimuli and show stimuli-responsive transport. I will show how we utilize such nanoparticle-blockage-induced stimuli-responsive transport to develop new applications for nanoparticle characterization, nanopore gating as well as bio-sensing.

Bio: Dr. Chuanhua Duan received his B.S. and M.S. degrees in Engineering Thermophysics from Tsinghua University in 2002 and 2004, respectively. He obtained his Ph.D. in Mechanical Engineering from the University of California at Berkeley in 2009 under the guidance of Prof. Arun Majumdar. After staying in Berkeley for two more years as a postdoctoral researcher at the Lawrence Berkeley National Laboratory, Dr. Duan joined the Department of Mechanical Engineering at Boston University as an assistant professor in 2012. He is currently an associate professor at BU ME, leading the Nanoscale Energy-Fluids Transport Laboratory. Among his honors, Dr. Duan received the Defense Advanced Research Project Agency Young Faculty Award (YFA) in 2018, the National Science Foundation Early Faculty Career Development Award (CAREER) in 2017, and the American Chemistry Society Petroleum Research Fund Doctoral New Investigator Award in 2013. His research focuses on the study of micro- and nanofluidic transport phenomena and the development of new fluidic devices/approaches for applications in healthcare, energy systems, and thermal management.

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Abstract: From tropical forests to gut microbiomes, ecological communities host striking numbers of coexisting species. Beyond high biodiversity, communities exhibit a range of complex dynamics that are difficult to explain under a unified framework. Using bacterial microcosms, we perform the first direct test of theory predicting that simple coarse-grained features dictate emergent behaviors of communities. As either the number of species or the strength of interactions increases, we show that microbial ecosystems transition between three distinct dynamical phases, from a stable equilibrium where all species coexist, to partial coexistence, to emergence of persistent fluctuations in species abundances, in the order predicted by theory. Under fixed conditions, high biodiversity and fluctuations reinforce each other. Our results demonstrate predictable emergent patterns of diversity and dynamics in ecological communities.

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Abstract: Response to pathogens and homeostasis is orchestrated by the complex interactions and activities of the large number of diverse cell types involved in the immune response. The innate immune response occurs soon after pathogen exposure and is carried out by phagocytic cells such as neutrophils or macrophages. The subsequent adaptive immune response involves antigen-presenting cells such as macrophages or dendritic cells; and antigen stimulation-dependent cell types such T cell subsets and B cells. As an alternative to polymers or hydrogels that are commonly used when model substrates are needed for uptake or migration studies from the point of view of mechanobiology, we developed ligand-functionalized lipid droplets to address these questions. In this talk, I will present how to make and characterize functional lipid droplets, how they can be used in the context of phagocytosis, cell migration and antigen extraction, and I will present the most recent ongoing results.

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Abstract: Intracellular delivery of biomolecules or nanomaterials is a critical step in many bioengineering processes across applications in science, technology, and medicine. In particular, emerging cell and gene therapies can require the genetic manipulation of extremely large numbers of cells (hundreds of trillions of cells, in some cases), and scale-up of conventional methods for delivering genetic material or gene editing complexes into cells (viral vectors, cationic polymers, electroporation) have faced issues with efficiency and/or cytotoxicity. In this talk, we will describe recent work developing a high-throughput method of intracellular delivery which used viscoelastic flow forces within a microfluidic chip to stretch and temporarily permeabilize the plasma membrane of cells, thereby enabling rapid and efficient delivery of large biomolecules including proteins, nucleic acids, and CRISPR-Cas ribonucleoprotein complexes to the cytosol. This method was notably fast, processing over 250 million cells per minute in a single microchannel (100x-1,000x faster than comparable methods) with up to 95% delivery efficiency. Altogether, viscoelastic mechanoporation seems to be a feasible method for high-throughput intracellular delivery for a range of different cell types that includes primary T and NK cells.

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Abstract:
Two recent projects from my lab that involve lineage trees of cells (the branching diagram that represents the ancestry and division history of individual cells). In the first project, we reconstructed the lineage trees of individual cancer cells from the patterns of randomly occurring mutations in these cells. We then inferred the age at which the cancer mutation first occurred and the rate of expansion of the population of cancer cells within each patient. To our surprise, we discovered that the cancer mutation occurs decades before diagnosis. For the second project, we developed microfluidic 'mother machines' that allow us to observe mammalian cells dividing across tens of generations. Using our observations, we calculated the correlation between the duration of cell cycle phases in pairs of cells, as a function of their lineage distance. These correlations revealed many surprises that we are trying to understand using hidden Markov models on trees. For both projects, I will discuss the mathematical challenges that we have faced and open problems related to inference from lineage trees.

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Abstract: The intersection between synthetic biology and materials science is an underexplored area with great potential to positively affect our daily lives, with applications ranging from manufacturing to medicine. My group is interested in harnessing the biosynthetic potential of microbes, not only as factories for the production of raw materials, but as fabrication plants that can orchestrate the assembly of complex functional materials. We call this approach “biologically fabricated materials”, a process whose goal is to genetically program microbes to assemble materials from biomolecular building blocks without the need for time consuming and expensive purification protocols or specialized equipment. Accordingly, we have developed Biofilm Integrated Nanofiber Display (BIND), which relies on the biologically directed assembly of biofilm matrix proteins of the curli system in E. coli. We demonstrate that bacterial cells can be programmed to synthesize a range of functional materials with straightforward genetic engineering techniques. The resulting materials are highly customizable and easy to fabricate, and we are investigating their use for practical uses ranging from bioremediation and biodegradable bioplastics to engineered therapeutic probiotics.

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Since its inception in 2004, the Microbial Science Initiative has sponsored and hosted an annual symposium for those in the Harvard and greater Boston communities. The spring event showcases magnificent research across a breadth of microbe-centric topics spanning environmental and biomedical sciences. The MSI Symposium is $20 for the public or $5 for students & postdocs. Welcome to the microbial world! Mid-morning and mid-afternoon breaks with refreshments will be provided, and there will be a 75 minute break for lunch mid-day.

Ticket registration required, $20 or $5 for Students & Postdocs, and is open to the public

Abstract:
When competing species grow into new territory, the population is dominated by descendants of successful ancestors at the expansion front. Successful ancestry depends on the reproductive advantage (fitness), as well as ability and opportunity to colonize new domains. (1) Based on symmetry considerations, we present a model that integrates both elements by coupling the classic description of one-dimensional competition (Fisher equation) to the minimal model of front shape (KPZ equation). Macroscopic manifestations of these equations on growth morphology are explored, providing a framework to study spatial competition, fixation, and differentiation, In particular, we find that ability to expand in space may overcome reproductive advantage in colonizing new territory. (2) Variations of fitness, as well as fixation time upon differentiation, are shown to belong to distinct universality classes depending on limits to gain of fitness.

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Abstract: Nanopores have gained a lot of attention recently for their ability to sequence nucleic acids. Recently, however, a surge of interest in the use of nanopores for analyzing proteins has been witnessed. I will talk about two approaches that our lab has taken for characterizing proteins. First, I will describe a method for full-length single-file protein translocation and discrimination using a biological pore. Second, I will describe a method for probing conformational states of a protein and its electrical unfolding. With these tools in mind, it is exciting to think about possibilities in using nanopores for studying protein variants, post-translational modifications, and interactions of proteins with small molecule drugs.

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Abstract: In various electro/biochemical processes, mechanical stress generation and transmission pathways exist in parallel and interact in concert with chemical reaction and mass diffusion pathways. How might the mechanics-electrochemistry reciprocity be harnessed for energy storage and energy harvesting, and unharnessed in battery degradation? Similarly, how might the mechanics-biochemistry crosstalk be regulated in development and repair, and dysregulated in disease and injury? These questions have been stimulating new understanding at the interfaces between mechanics and other disciplines including materials, chemistry, biology, and medicine. In this talk, I will show a set of exciting phenomena in rechargeable batteries and living organisms to highlight the crosstalks. Emphasis will be placed on the fundamental mechanics linking to bio/electrochemistry, which underlies materials design, energy storage and harvesting, disease control, and nanomedicine innovation.

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Pangenome analysis has become a vital tool to understand bacterial diversity. In this Chalk Talk, we will discuss how we can interpret a pangenome from an ecological perspective to explore the evolution of microorganisms.

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Abstract:
The sizes of many subcellular structures are coordinated with cell size to ensure that these structures meet the functional demands of the cell. In eukaryotic cells, these subcellular structures are often membrane-bound organelles, whose volume is the physiologically important aspect of their size. Scaling organelle volume with cell volume can be explained by limiting pool mechanisms, wherein a constant concentration of molecular building blocks enables subcellular structures to increase in size proportionally with cell volume. However, limiting pool mechanisms cannot explain how the size of linear subcellular structures, such as cytoskeletal filaments, scale with the linear dimensions of the cell. Recently, we discovered that the length of actin cables in budding yeast (used for intracellular transport) precisely matches the length of the cell in which they are assembled. Using mathematical modeling and quantitative imaging of actin cable growth dynamics, we found that as the actin cables grow longer, their extension rates slow (or decelerate), enabling cable length to match cell length. Importantly, this deceleration behavior is cell-length dependent, allowing cables in longer cells to grow faster, and therefore reach a longer length before growth stops at the back of the cell. In addition, we have unexpectedly found that cable length is specified by cable shape. Our imaging analysis reveals that cables progressively taper as they extend from the bud neck into the mother cell, and further, this tapering scales with cell length. Integrating observations made for tapering actin networks in other systems, we have developed a novel mathematical model for cable length control that recapitulates our quantitative experimental observations. Unlike other models of size control, this model does not require length-dependent rates of assembly or disassembly. Instead, feedback control over the length of the cable is an emergent property due to the cross-linked and bundled architecture of the actin filaments within the cable. This work reveals a new strategy that cells use to coordinate the size of their internal parts with their linear dimensions. Similar design principles may control the size and scaling of other subcellular structures whose physiologically important dimension is their length.

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Is there an item that's been languishing on your to-do list? Do you have an assignment to do and just can't harness the motivation to take the first step? Register and join the Microbial Sciences Initiative for a Micro-Goal Lunch Hour! Open to all Harvard students and postdocs, especially those with an interest in the microbial world.

Abstract: TBD

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Abstract:
Motivated by the existence of membrane-less compartments in the chemically active environment of living cells, I will discuss the dynamics of droplets in the presence of active chemical reactions. Therefore, I will first introduce the underlying interplay between phase separation and active reactions, which can alter the droplet dynamics compared to equilibrium systems. A key feature of such systems is the emergence of concentration gradients even at steady states. In the second part of this talk, I will discuss how these gradients can trigger instabilities in the core of chemically active droplets, giving rise to a new non-equilibrium steady state of liquid spherical shells. Finally, I will present experimental and theoretical results discussing the existence and energetic cost of this non-equilibrium steady state in a coacervate system.

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TBD

Abstract: This talk will introduce concepts of targeted photodynamic therapy with microscale fidelity using clinical antibody–photosensitizer (benzoporphyrin derivative monoacid A, verteporfin) conjugates. These initially quenched (“off”) photoimmunoconjugates target tumor cell-surface biomarkers and become activated upon cell-internalization ("on"). Present efforts to further develop these concepts for precision treatment of heterogenous human ovarian cancer will be discussed.

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Invited Speakers:
Corey O'Hern, Yale University
Leslie Shor, University of Connecticut
Ian Wong, Brown University
Evan Wujcik, University of Maine

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Abstract:
Morphogenesis, the process through which genes generate form, establishes tissue scale order as a template for constructing the complex shapes of the body plan. The extensive growth required to build these ordered substrates is fueled by cell proliferation, which, naively, should disrupt order. Understanding how active morphogenetic mechanisms couple cellular and mechanical processes to generate order remains an outstanding question in animal development. I will review the statistical mechanics of orientational order and discuss the observation of a fourfold orientationally ordered phase (tetratic) in the model organism Parhyale hawaiensis. I will also discuss theoretical mechanisms for the formation of orientational order that require both motility and cell division, with support from self-propelled vertex models of tissue. The aim is to uncover a robust, active mechanism for generating global orientational order in a non-equilibrium system that then sets the stage for the development of shape and form.

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Abstract: TBD

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Is there an item that's been languishing on your to-do list? Do you have an assignment to do and just can't harness the motivation to take the first step? Register and join the Microbial Sciences Initiative for a Micro-Goal Lunch Hour! Open to all Harvard students and postdocs, especially those with an interest in the microbial world.

Abstract: Photocrosslinkable polymers are polymers that can be solidified from liquid upon light exposure. They have been employed to fabricate tissue engineered constructs due to the mild conditions for crosslinking, highly tunable mechanical and structural modifiability, printability, biodegradability and biocompatibility. These biomaterials can maintain their structural integrity after biofabrication and provide topological, biochemical, and physical cues to guide cellular behaviors by creating a biomimetic microenvironment.

The emphasis of this talk is placed on how photocrosslinkable polymers can be used to achieve tissue regeneration, for example, their fabrication into various scaffolds (electrospun fibers, microspheres, and 3D printed scaffolds) to reconstruct bones. Specifically, assisted by microfluidics, we have developed photocrosslinkable methacrylated gelatin (GelMA) based microspheres encapsulating human mesenchymal stem cells (MSCs) for bone repair. Due to the mild crosslinking conditions, we found that the GelMA microspheres can provide a favourable micro-environment for MSC survival, spreading, migration, proliferation and osteogenesis. In another study, we prepared a periosteum mimicking bone aid (PMBA) by electrospinning photocrosslinkable GelMA with L-arginine-based unsaturated poly(ester amide) (Arg-UPEA), and methacrylated hydroxyapatite nanoparticles (nHAMA). Upon light exposure, the resultant hydrogel fibrous scaffolds can solidify within seconds. Via controlling the crosslinking density, we can control the scaffolds’ mechanical and degradation property. The optimal scaffold was found to provide long term structural and functional support and mediation of physiological activity. With the aid of 3D printing, we developed 3D bone scaffolds made of photocrosslinkable nanocomposite ink consisting of tri-block poly (lactide-co-propylene glycol-co-lactide) dimethacrylate (PmLnDMA, m and n respectively represent the unit length of propylene glycol and lactide) and nHAMA. It is discovered that nHAMA can rapidly interact with PmLnDMA upon light exposure within 140 seconds and form an inorganic-organic co-crosslinked nanocomposite network. This bone ink was found to provide good mechanical support and bioactivity (allow for encapsulation and long-term release of growth factors) for bone regeneration.

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Abstract: The displacement of one fluid by another immiscible fluid in confined geometries occurs in many natural and industrial settings from geological CO₂ sequestration to microfluidics. The fluid-solid interactions are key to understanding the combined effects of wetting, capillarity and viscous forces, which, in turn, control the fluid-fluid displacement patterns. One fundamental aspect of fluid-fluid displacement in confined geometries is the wetting transition: the displacement rate above which films of the defending fluid are deposited on the confining surfaces. These films may later dewet, giving rise to complex “residual fluid” patterns. Earlier experiments in our group have shown that the wetting transition results in interface pinch-off that generates disconnected bubbles and drops even in uniform capillaries without external crossflow (Zhao et al., PRL 2018). Here I will present a phase-field model to simulate the two-phase flow with moving contact lines and investigate the interface dynamics in a smooth confinement over a wide range of wettability conditions and viscosity contrast. I will show that the pinch-off of a bubble only occurs when the invading fluid is less viscous. Since real surfaces are rough, we investigate the role of wall roughness on two-phase displacements in confined geometries by means of experiments on a microfluidic fracture with precisely-controlled structured surface. We show that the roughness induces two types of liquid films entrained on the solid surfaces: the classical Bretherton “thick film”, and a new type of “thin film” that is confined within the roughness. Each type is characterized by distinct stability criteria and dewetting dynamics. Our work shed light on the microscale physics and macroscopic displacement patterns in confined geometries that may control long-term biogeochemical reactions.

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Abstract:
Over the last two decades, major progress has been made in understanding the self-organization principles of active matter. A wide variety of experimental model systems, from self-driven colloids to active elastic materials, has been established, and an extensive theoretical framework has been developed to explain many of the experimentally observed non-equilibrium pattern formation phenomena. Two key challenges for the coming years will be to translate this foundational knowledge into functional active materials, and to identify quantitative mathematical models that can inform and guide the design and production of such materials. Here, I will describe joint efforts with our experimental collaborators to realize self-growing bacterial materials [1], and to implement computational model inference schemes for active and living systems dynamics [2,3].

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The World Health Organization estimates that agricultural productivity will need to increase by 70% by 2050 to meet the food needs of a global population of 10B people. Facing a changing climate and increasing disease pressure, growers today spend nearly $80B on six billion pounds of pesticides each year, and yet still experience yield losses of 20-40% due to pests and disease. Broad-acting, chemically derived pesticides - currently the industry standard - are losing both efficacy and public support as resistance spreads and their negative environmental impacts become clear. At Robigo, we believe in building on nature’s foundation to engineer solutions that work for growers, consumers, and the environment. We have developed a scalable plug and play platform technology that leverages synthetic biology, CRISPR, and data science to engineer microbes that are naturally found out in the fields to protect crops, fight disease, and improve overall yields. Initially targeting three diseases that affect citrus, apples, and tomatoes, our microbes outperform commercial chemical pesticides and reduce disease by over 90% while increasing plant biomass by over 15%. Robigo is unlocking the potential of engineered microbes in agriculture to fundamentally change how the world grows food and create a more sustainable future for agriculture. Founded by MIT synthetic biologists, Robigo is a VC-backed, Seed-stage biotech startup based in Cambridge, MA.

Abstract: Sediment transport caused by particles rolling, sliding, and hopping on a river bed is called bedload transport. Semi-empirical formulas to predict bedload sediment flux from the driving factors, known as the transport relation, can be highly inaccurate. Simulations where the sediment particles are fully resolved are carried out to find if the predictions can be improved by considering more particle parameters. After being validated against flume experiments, the numerical scheme is used to simulate bedload transport under many conditions, and its results show that at a fixed relative hydrodynamic driving force, varying river slope (on gentle slopes), fluid depth, mean particle size, particle surface sliding friction coefficient, and grain-grain damping coefficient cause almost no variation of the transport rate. The simulations also shed light on the microscopic mechanisms such as how the fluid torque on particles helps initiate rolling and subsequent grain transport. We further use the numerical scheme to guide development of an alternative framework that can predict the flow profiles for the fast transport as well as the gradual transport beneath the bed surface without resolving the individual particles, which is a more tractable way to model large-scale bedload sediment transport problems.

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Thursday, February 9, Lecture 1:
A brief intro to protein biology. AlphaFold2 impacts on experimental structural biology. Co-evolutionary approaches. Space of ‘algorithms’ for protein structure prediction. Proteins as images (CNNs for protein structure prediction). End-to-end differentiable approaches. Attention and long-range dependencies. AlphaFold2 in a nutshell.

Thursday, February 16, Lecture 2:
AlphaFold2 architecture. Turning the co-evolutionary principle into an algorithm: EvoFormer. Structure module and symmetry principles (equivariance and invariance). OpenFold: retraining AlphaFol2 and insights into its learning mechanisms and capacity for generalization. Applications of variants of AlphaFold2 beyond protein structure prediction: AlphaFold Multimer for protein complexes, RNA structure prediction.

Thursday, March 9, Lecture 3:
Limitations of AlphaFold2 and evolutionary ML pipelines. Current single sequence models. Protein language models (LM): single sequence + LM embeddings. Combining LM models with Frenet-Serret construction for protein structure prediction. Applying AlphaFold2 and OpenFold for language models.

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Is there an item that's been languishing on your to-do list? Do you have an assignment to do and just can't harness the motivation to take the first step? Register and join the Microbial Sciences Initiative for a Micro-Goal Lunch Hour! Open to all Harvard students and postdocs, especially those with an interest in the microbial world.

Abstract: I will focus on the interaction between different active matter systems. In particular, I will describe recent experimental and modeling results that reveal how interaction forces between adhesive cells generate activity in the cell layer and lead to a potentially new mode of phase segregation. I will then discuss mechanics of how cells use finger-like protrusions, known as filopodia, to interact with their surrounding medium. First, I will present experimental and theoretical results of active mirror-symmetry breaking in subcellular skeleton of filopodia that allows for rotation, helicity, and buckling of these cellular fingers in a wide variety of cells ranging from epithelial, mesenchymal, cancerous and stem cells. I will then describe in-vivo experiments together with theoretical modeling showing how during embryo development specialized active cells probe and modify other cell layers and integrate within an active epithelium.

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A major portion of microbial life on Earth is present in low-temperature/deep-sea environments, and yet much remains to be learned of their diversity, adaptations and activities. Studies of these microbes in situ and ex situ is providing fundamental and biotechnological insights, and will be critical to many possible ocean-based decarbonization processes. In this presentation I will first discuss what we have learned about proteomes and cell envelopes of piezophilic (high pressure-adapted) isolates. Then I will transition to investigations of deep-sea microbial activities using pressure-retaining seawater sampling to collect microbes with minimal temperature/pressure alteration, followed by the sorting and identification of cells active under in situ deep-sea conditions. One aspect of this work is the indication that certain microbial groups (e.g., members of the Thaumarchaeota) are highly sensitive to decompression/incubation effects, reducing their perceived significance when collected using standard methods.
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Abstract: Halide perovskites are an emerging class of low-cost solution-processable semiconductors that have recently demonstrated exceptional performance when employed in optoelectronic devices like solar cells or light-emitting diodes (LEDs) for displays. Yet, we don't understand how these materials can work so very efficiently, given the presence of structural disorder and electronic traps, compared to highly crystalline silicon currently produced at scale under energy-extensive conditions. I will discuss our latest mechanistic insights from spectroscopy on both 3D (bulk) halide-perovskite thin-films as well as quantum-confined and doped 0D colloidal nanocrystals, enabling highly efficient flexible solar cells and ultra-bright displays. We find that energetic disorder and local structural symmetry breaking are key for explaining our observations.

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Abstract: Nanostructured materials can be designed with sophisticated features to fulfill the complex requirements of advanced material applications. Our laboratory has developed organic and inorganic nanoparticles and nanocomposites for advanced drug delivery, antimicrobial, stem cell culture, and tissue engineering applications. In addition, we have nanofabricated microfluidic systems for drug screening, in vitro toxicology, and diagnostic applications. The nanosystems allow for the rapid and automated processing of drug candidates and clinical samples in tiny volumes, greatly facilitating drug testing, genotyping assays, infectious disease detection, point-of-care monitoring, as well as cancer diagnosis and prognosis.

We have also synthesized metallic, metal oxide, and semiconducting nanoclusters, nanocrystals and nanosheets of controlled dimensions and morphology. The nano-sized building blocks are used to create multifunctional systems with excellent dispersion and unique properties. Nanoporous materials of a variety of metal oxide and organic backbone have also been created with high surface areas and well-defined porosities. These nanostructured materials are successfully tailored towards energy and sustainability applications.

Speaker Bio:
Jackie Y. Ying received her Ph.D. from Princeton University. She was Professor of Chemical Engineering at MIT (1992-2005), and Founding Executive Director of Institute of Bioengineering and Nanotechnology, Singapore (2003-2018). She is currently A*STAR Senior Fellow and Director of NanoBio Lab, Institute of Materials Research and Engineering and A*STAR Infectious Diseases Labs.

For her research on nanomaterials and bioengineering, Prof. Ying has been recognized with the American Ceramic Society Purdy Award, David and Lucile Packard Fellowship, ONR Young Investigator Award, NSF Young Investigator Award, Camille Dreyfus Teacher-Scholar Award, ACS Faculty Fellowship Award in Solid-State Chemistry, Technology Review's Inaugural TR100 Young Innovator Award, AIChE Colburn Award, International Union of Biochemistry and Molecular Biology Jubilee Medal, Mustafa Prize "Top Scientific Achievement Award," Turkish Academy of Sciences Academy Prize in Science and Engineering Sciences, and Journal of Drug Targeting's Lifetime Achievement Award.

Prof. Ying is an elected Member of the German National Academy of Sciences-Leopoldina, and U.S. National Academy of Engineering. She is a Fellow of MRS, RSC, AIMBE, AAAS, and U.S. National Academy of Inventors. She was the Founding Editor-in-Chief of Nano Today.

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Abstract: The underlying molecular mechanism of autism, a known example of neurodiversity, remains largely unknown, with cognitive differences providing the main means of diagnosis. I would like to make an argument for the connection between neurodiversity and the emergence of aberrant viscoelastic properties of the extracellular matrix in the central nervous system. A mechanical interplay like this can enable us with a diagnosis based on a measurable physiological feature: the mechanical fingerprint of our tissues.

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Presenters:
Pia Leon (@pialeonkjolle) Chef and Co-owner of Kjolle, Central (Lima, Perú), MIL (Cusco, Perú), World's Best Female Chef of 2021

Malena Martinez (@malenamater) Co-Director of Mater Iniciativa, Central

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Abstract: My lab is developing biophysical methods to achieve multicolor and dynamic biological imaging at the molecular scale. Our approach to capturing the dynamics of cellular processes involves cryo-vitrifying samples after known time delays following stimulation using custom cryo- plunging and high-pressure freezing instruments. To achieve multicolor electron imaging, we are exploring the property of cathodoluminescence—optical emission induced by the electron beam. We are developing nanoprobes ("cathodophores") that will be used as luminescent protein tags in electron microscopy. We are applying these new methods to study G-protein - coupled receptor signaling and to visualize the formation of biomolecular condensates.

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Abstract: Over the last decade there has been growing evidence demonstrating that dense biological tissue can spontaneously undergo transitions between a solid-like (jammed) state and a fluid-like (unjammed) state. The rheological state of the tissue in turn influences the transmission of mechanical deformations, which plays a central role in driving developmental processes, such as wound healing and morphogenesis, and tumor progression. Using computational models and analytical approaches, we have investigated the linear and nonlinear constitutive equations of confluent tissue, with no gaps between cells, under shear deformations. We find that an initially undeformed fluid-like tissue acquires finite rigidity above a critical applied strain and that solid-like tissue quickly exhibit nonlinear stress-strain response. We formulate a continuum model that couples cell shape to flow and captures both the tissue solid-liquid transition and its rich linear and nonlinear rheology.

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Abstract: There are many situations where active fluids coexist with passive ones. In bacterial swarms internal boundaries form separating cells of different type or separating live and dead cells. In cell biology the evidence for the formation of membraneless organelles has fueled interest in the role of active processes in liquid-liquid phase separation. Inspired by recent experiments that combine a microtubule-based active fluid with an immiscible binary polymer mixture, we have used numerical and analytical methods to explore how active stresses and associated flows modify the properties of the soft interfaces in a phase separating mixture. Experiments and theory have revealed a wealth of intriguing phenomena, including giant interfacial fluctuation, traveling interfacial waves, activity suppressed phase separation, and activity controlled wetting transitions.

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Presenter: Tracy Chang (@gopagu) Pagu Restaurant (Cambridge, MA)

Abstract: Birds flock, bees swarm and fish school. These are just some of the remarkable examples of collective behavior found in nature. Physicists have been able to capture some of this behavior by modeling organisms as "flying spins'' that align with their neighbors according to simple but noisy rules. Successes like these have spawned a field devoted to the physics of active matter - matter made not of atom and molecules but of entities that consume energy to generate their own motion and forces. Through interactions, collectives of such active particles organize in emergent structures on scales much larger than that of the individuals. There are many examples of this spontaneous organization in both the living and non-living worlds: motor proteins orchestrate the organization of genetic material inside cells, swarming bacteria self-organize into biofilms, epithelial cells migrate collectively to fill in wounds, engineered microswimmers self-assemble to form smart materials. In this lecture I will introduce the field of active matter and highlight ongoing efforts by physicists, biologists, engineers and mathematicians to model the complex behavior of these systems, with the goal of identifying universal principles.

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Abstract: We investigate the ground-state configurations of two-dimensional liquid crystals with p-fold rotational symmetry (p-atics) on cones. The cone apex develops an effective topological charge, which in analogy to electrostatics, leads to defect absorption and emission at the cone apex as the deficit angle of the cone is varied. We find three types of ground-state configurations as a function of cone angle, which is determined by charged defects screening the effective apex charge: (i) for sharp cones, all of the +1/p defects are absorbed by the apex; (ii) at intermediate cone angles, some of the +1/p defects are absorbed by the apex and the rest lie equally spaced along a concentric ring on the flank; and (iii) for nearly flat cones, all of the +1/p defects lie equally spaced along a concentric ring on the flank. We check these results with numerical simulations for a set of commensurate cone angles and find excellent agreement.

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Is there an item that's been languishing on your to-do list? Do you have an assignment to do and just can't harness the motivation to take the first step? Join the Microbial Sciences Initiative for a Micro-Goal Lunch Hour! Come with a task that is reachable in about 45 minutes - like answering an email or two, writing a paragraph, reading a chapter, or organizing a dataset. It doesn't have to be Microbiology-related, but if it is, we can help!
Register for the Micro-Goal Hour

Abstract: Biological systems can create complex self-limited structures, such as viral capsids and microtubules, by controlling the valence and binding angles of biomolecular interactions. Inspired by this strategy, we create DNA origami subunits with specific interactions and prescribed binding angles that assemble into tubules whose self-limited width is much larger than the subunit size. Although we target a single tubule geometry, we find that thermal fluctuations can produce a variety of assemblies close to the target structure. This challenge is compounded by the fact that specific, valence-limited interactions localize subunit binding and limit their mobility within an assembly. Therefore, the tubule structures are unable to relax to equilibrium even as they continue to grow. To circumvent this challenge, we consider two routes for reducing polymorphism in the final assemblies: (i) increasing the assembly complexity to remove states close to the target and (ii) designing soft directions in the assembly that allow the tubules to anneal towards their equilibrium structure. I will show some recent experimental results highlighting the potential for both of these strategies. These results show how including degrees of freedom for assemblies to avoid or anneal out of kinetics traps can help reduce polymorphism as we strive to make more complex structures.

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Presenter:
Eduard Xatruch (@disfrutarbcn) Disfrutar and Compartir Barcelona

Abstract: Enzymes are highly specific catalysts delivering improved drugs and greener industrial processes. Naturally occurring enzymes must typically be optimized which is often accomplished through directed evolution based on error prone PCR; however, this method limits exploration of fitness landscape to only evolutionary favored amino acid substitutions and results in high number of silent mutations. We develop a new library preparation method based on overlapping oligo pools and gene recombination to enable introduction of all possible substitutions at each position with highly controllable mutation rates. While conventional highest throughput methods for screening of enzyme libraries are limited by throughput of microfluidic devices and E. coli transformation efficiency to 107-8 variants, we leverage in vitro transcription and translation in a combination with multiple consecutive microfluidics-based sorting to screen libraries with more than 1012 variants. We combine new library preparation and screening methods to convert lipase into a protease in a single mutagenesis step.

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Presenter:
Sean Sherman (@the_sioux_chef), Chef, Founder of The Sioux Chef, Co-Founder of NĀTIFS (North American Traditional Indigenous Food Systems), Co-Owner of Owamni by The Sioux Chef

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Presenter:
Bryan Furman (@bs_pitmaster), Pitmaster, Bryan Furman BBQ, B's Cracklin Barbecue, Chef in Residence at Stone Barns Center for Food & Agriculture

Abstract: Modeling multiphase flow in subsurface formations such as aquifers and hydrocarbon reservoirs is a challenging task with many open questions. An important tool for investigating these flows on the laboratory scale are coreflooding exeriments conducted on rock samples (cores) extracted from reservoirs. Coreflooding experiments with computed tomography (CT) imaging are becoming common practice. They allow to investigate the sub-core scale properties such as relative permeability and capillary pressure, and to construct multiphase flow models that not only capture the core average flow, but also the flow on the sub-core (millimeter) scale. These core flow models are important for a number of reasons. First, they allow to evaluate the applicability of mathematical models and numerical simulators. Second, coreflooding models can be applied towards forecasting, therefore replacing experiments. Finally, models can be used for relating between sub-core scale properties and core effective properties, which can provide insight on upscaling and used in developing upscaling methods for larger scales. In this presentation, we will discuss results of recent work on modelling both drainage and imbibition coreflooding experiments and methods for estimating properties on both core and sub-core scales. Experimental data of three-dimensional saturation distribution, capillary pressure measurements and core pressure drop will be presented. The core properties will be estimated using various different models and simulation results will be compared to the data.

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Presenter:
Kate Strangfeld (@kate_cooks, @bitescizededucation), Founder of Bite Scized Education, Former Middle School Science and Chemistry Teacher, Washington International School
*This is a special session for teachers, educators, or anyone who is interested in using food to teach science

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Abstract: The viscoelastic nature of soft materials, such as polymers and biomaterials, is a significant challenge in their mechanical characterization due to the strong dependence of their properties on strain rate. Young's modulus is a well understood elastic constant for metals but less so for many soft materials. Especially, the long chain molecules may deform by triggering mechanisms such as chain bending, sliding, and rotation rather than loading of primary bonds at small strains. This talk will discuss the applicability of the existing time and frequency domain characterization methods to soft materials with the aim of developing a correspondence between the elastic and viscoelastic properties. Many assumptions such as small deformation, constant Poisson's ratio and large aspect ratio of the specimens, inherent to the conventional test method, are violated in soft materials and need to be compensated for. The effect of these parameters is examined as well as a transform is developed to convert the frequency domain measurements to time domain to account for the strain rate sensitivity.

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Dr. Jacinta Conrad, Associate Professor, University of Houston
Abstract: The dispersity, or breadth in the molecular weight distribution, is an inherent feature of synthetic polymer systems. Typically treated as an unfortunate consequence of polymer synthesis, here I will discuss how polymer dispersity can be tuned to generate novel function in bulk and interfacial properties. In bulk systems, I will show that both the shear and extensional rheology of mixtures of colloids and non-adsorbing polymers, a common model system for feedstocks for 3-D printing and coating, depend on the polymer dispersity. In interfacial systems, I will show how shaping the molecular weight distribution of surface-grafted polymer brushes can modulate both brush structure and stimulus response. Thus, molecular weight distributions represent an intriguing route for tailoring polymer properties.

Presenter:
Fatmata Binta (@chef_binta) Chef of "Dine on a Mat" and Founder of Fulani Kitchen Projects

Abdullah Bannan
CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA

Jimena Luque
Assessment of possible concerted chromosome loss in yeast

Llinca Mazureac
Growth rate regulation in rod shaped bacteria

Register for the Chalk Talk

Abstract: We are developing systems, structures, and machines that can perform complex tasks or exhibit intelligence in response to external stimuli all using bio-inspired materials. Inspired by systems spanning from how tissues build themselves to how animals camouflage, I will discuss our molecular-level approach to building new materials that can produce controllable transformations in response to specific chemical inputs for applications ranging from colorimetric sensors to implantable electronics.

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Presenter:
Chintan Pandya (@chefchintan) Chef and Partner of Unapologetic foods including Dhamaka, Adda, and Semma

Presenter:
Arielle Johnson, Ph.D. (@arielle_johnson) Flavor Scientist, Gastronomy and Innovation Researcher, Co-founder of the Noma Fermentation Lab

Abstract: Natural materials offer new avenues for innovation across fields, bringing together, like never before, natural sciences and high technology. Significant opportunity exists in reinventing naturally-derived materials, such as structural proteins, and applying advanced material processing, prototyping, and manufacturing techniques to these ubiquitously present substances. This approach help us imagine and realize sustainable, carbon-neutral strategies that operate seamlessly at the interface between the biological and the technological worlds. Some of these opportunities include biomaterials-based applications in edible and implantable electronics, food preservation, energy harvesting, wearable sensors, compostable technology, distributed environmental sensing, medical devices and therapeutics, biospecimen stabilization, advanced medical diagnostics, and will be outlined in this talk.

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Presenter:
Joanne Chang '91 (@jbchang), Flour Bakery and Café, Myers + Chang, author of "Flour", "Flour Too", "Myers + Chang at Home", and "Baking With Less Sugar"

Abstract: Sleep emerged in early animals and is ubiquitous today. No explanation could be found for why this behavior is essential for survival. We recently discovered that when sleep is prevented, the organ most critically injured is the gut - gut dysfunction can even explain why severe sleep loss can be lethal. More recently we found that the relationship between sleep and the gut is bidirectional, with a gut-derived signal regulating sleep depth. I will discuss these and related results which argue that sleep should not be studied only from a brain-centric perspective.

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Abstract: Based on cell unjamming we derive a cell motility marker for static histological images. This enables us to sample huge numbers of breast cancer patient data to derive a comprehensive state diagram of unjamming as a collective transition in cell clusters of solid tumors. As recently discovered, cell unjamming transitions occur in embryonic development and as pathological changes in diseases such as cancer. No consensus has been achieved on the variables and the parameter space that describe this transition. Cell shapes or densities based on different unjamming models have been separately used to describe the unjamming transition under different experimental conditions. Moreover, the role of the nucleus is not considered in the current unjamming models. Mechanical stress propagating through the tissue mechanically couples the cell nuclei mediated by the cell's cytoplasm, which strongly impacts jamming.

Based on our exploratory retrospective clinical study with N=1,380 breast cancer patients and vital cell tracking in patient-derived tumor explants, we find that the unjamming state diagram depends on cell and nucleus shapes as one variable and the nucleus number density as the other that measures the cytoplasmic spacing between the nuclei. Our approach unifies previously controversial results into one state diagram. It spans a broad range of states that cancer cell clusters can assume in a solid tumor. We can use an empirical decision boundary to show that the unjammed regions in the diagram correlate with the patient's risk for metastasis.

We conclude that unjamming within primary tumors is part of the metastatic cascade, which significantly advances the understanding of the early metastatic events. With the histological slides of two independent breast cancer patients' collectives, we train (N=688) and validate (N=692) our quantitative prognostic index based on unjamming regarding metastatic risk. Our index corrects for false high- and low-risk predictions based on the invasion of nearby lymph nodes, the current gold standard. Combining information derived from the nodal status with unjamming may reduce over- and under-treatment.

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Presenters:
Dave Arnold (@CookingIssues), Booker and Dax, author of "Liquid Intelligence", host of "Cooking Issues," founder of the Museum of Food and Drink
Harold McGee (@Harold_McGee), author of "On Food and Cooking", "Curious Cook", "Nose Dive: A Field Guide to the World's Smells"

Abstract: Bandages, glues, and stickers are commonly seen bioadhesives that are used extensively in the clinics and our daily lives. However, they usually have weak adhesion on wet biological tissues, and are challenging to control precisely the location, strength and duration of the formed adhesion. We report an ultrasound (US)–mediated strategy to achieve tough bioadhesion with controllability and fatigue resistance. Without chemical reaction, the US can amplify the adhesion energy and interfacial fatigue threshold between hydrogels and porcine skin by up to 100 and 10 times. Combined experiments and theoretical modeling suggest that the key mechanism is US-induced cavitation, which propels and immobilizes anchoring primers into tissues with mitigated barrier effects. Our strategy achieves spatial patterning of tough bioadhesion, on-demand detachment, and transdermal drug delivery. This work expands the material repertoire (polymers, nanoparticles and proteins) for tough bioadhesion and enables bioadhesive technologies with high-level controllability. The universal applicability of our strategy promises impacts in broad areas ranging from wearable devices to drug delivery.

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About: As COVID-19 continues to remind us, significant gaps and exceedingly difficult scientific and translational challenges must be addressed to better prepare, mitigate, and face epidemics and global pandemics, that are bound to continue to occur with all the associated global economic and human life costs. These challenges cannot be left to be solved in a few months once a pandemic starts. Solid and deep scientific foundations, built over continued and sustained efforts, are required; and such challenges simply cannot be tackled by isolated, traditional fields of research.

This 2022 Gordon Research Conference brings together experts from a range of synergistic and complementary disciplines (mathematics/physics, engineering, microbiology/virology, epidemiology) to exchange on frontier research in health, including respiratory/nosocomial infectious diseases transmission and public health, where bio- and fluid physics are at the core.

The fantastic line-up of participants covers a wide range of fields to continue our 2019 effort to build a sustained and solid intellectual foundation and connected community. Thought and program leaders come together with young researchers to address the subtle and complex challenges of the growing intersection between fluid physics, biophysics, soft matter, infectious diseases and contamination across scales.

Note that applicants for posters or attendance can be in areas that are much broader than "infectious disease transmission." Similarly to the F&H 2019 conference, this GRC 2022 iteration will involve discussions on technical, theoretical, methodological, and translational challenges relevant for a range of open scientific questions at the intersection of virology/microbiology/physiology/mechanics/fluid mechanics, biophysics/soft matter, mixing/soft matter/applied math/modelling and health broadly defined. So those in these areas should also consider applying for the posters and attendance!

Please apply before attending

Abstract: The human heart is made up of helically aligned myofibers, with the left ventricle transitioning from a left- to right-handed helix across the septal wall. For more than half a century, it has been argued that this helical arrangement is critical for achieving physiologically relevant ejection fractions, however testing this fundamental assumption has been difficult. While surgical corrections can affect slight changes over these tissue alignments in animal studies, these are often characterized by concomitant changes in protein expression and metabolism. This makes it difficult to delineate their biophysical and biochemical effects on cardiac health. Conversely, in vitro studies have difficulty reproducing these complex architectures, including helical cardiomyocyte alignment. To address these challenges, here we introduce a novel additive textile manufacturing approach, Focused Rotary Jet Spinning (FRJS), which allows for the rapid manufacturing of micro/nanofibers scaffolds with controlled alignments and helical architectures. Using these scaffolds to control tissue morphogenesis and alignment, we demonstrate the biofabrication of in vitro cardiac ventricle models with controlled helical and circumferential alignments. With their aligned tissue structures, these models can preserve some clinically relevant features of ventricle performance, including ventricle twist, and increased apical to base conduction velocities. Using these models, we show that helically aligned ventricles display increased, axial shortening, cardiac output, and ejection fractions when compared to circumferential alignments. This shows that cardiac tissue alignment is an important regulator of ventricular performance in three-dimensional (3D) tissue-scaffolds, and confirms fundamental theoretical predictions regarding cardiac physiology made over fifty years prior. Overall, this work suggests that FRJS may serve as a valuable tool for future biofabrication, and may be used as a potential alternative, or in conjunction with more traditional approaches such as 3D bioprinting.

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About: Have you ever found yourself renaming files as script.py, script_mod.py, script_final.py, and then script_final2.py, script_really_final.py? If so, this course is for you! By the end of this interactive workshop, you will know how to harness the power of version control to keep track of file changes and data in a safe and consistent way. The tools for the job will be Git and GitHub allowing you to organize both simple and complex code projects as well to make teamwork and collaborations easy and effective.

• Setting up a (local) repository
• Adding, committing, stashing, reverting, resetting...
• Branching, merging
• Example of best practices (e.g. tracking code vs ignoring large output data)
• Remote vs local branches
• Pull requests and merging
• Forking
• Issues
• Project planning
• Wiki

Instructors: Giovanni Bordiga, Eder Medina, Louis-Justin Tallot and Florent Pollet
The meeting will have two sessions, each will last 50 minutes.
Session 1: 11:00 - 11:50 AM
Session 2: 12:00 - 12:50 PM
Lunch: 1:00 PM

About: The short course is designed for the quick introduction for flow visualization techniques including shadowgraphy, Schlieren, and particle image velocimetry. The course is organized in three sessions over 3 hours.

For the first lecture, we will talk about shadowgraphy and Schlieren methods that are the method to detect the difference of the refractive index in fluid media. By using the distortion of the light ray through a different fluid, we can observe the motion of fluid.

Secondly, the most conventional flow visualization technique will be introduced, so-called particle image velocimetry (PIV). In this lecture, to perform PIV, three main aspects are discussed, particle, light source, and optics. Furthermore, the optimal conditions for achieving a good vector field are summarized and explained.

Lastly, we will shortly discuss micro-PIV, which is for microfluidics applications. Some distinct features compared to conventional PIV are treated during the lecture.

The meeting will have three sessions, each will last 50 minutes.
Session 1: 10:00 - 10:50 AM
Session 2: 11:00 - 11:50 AM
Lunch: 12:00 - 1:00 PM
Session 3: 1:00 - 1:50 PM

Please register before attending

About: Learn about the latest in confocal microscopy from Leica Instruments during this demonstration of the Stellaris 8 by Leica Instruments.

About the Leica Stellaris 8 Confocal Demonstration

Abstract: Biological processes, from morphogenesis to tumor invasion, spontaneously generate shear stresses inside living tissue. The mechanisms that govern the transmission of mechanical forces in epithelia and the collective response of the tissue to bulk shear deformations remain, however, poorly understood. Using a minimal cell-based computational model, we investigate the constitutive relation of confluent tissues under simple shear deformation. We show that an initially undeformed fluidlike tissue acquires finite rigidity above a critical applied strain. This is akin to the shear-driven rigidity observed in other soft matter systems. Interestingly, shear-driven rigidity can be understood by a critical scaling analysis in the vicinity of the second order critical point that governs the liquid-solid transition of the undeformed system. We further show that a solidlike tissue responds linearly only to small strains and then switches to a nonlinear response at larger stains, with substantial stiffening. Finally, we propose a mean-field formulation for cells under shear that offers a simple physical explanation of shear-driven rigidity and nonlinear response in a tissue.

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Abstract: Large floating viscous bubbles whose interior gas is rapidly depressurized exhibit a remarkable dynamics, characterized by a periodic pattern of radial wrinkles that permeate the liquid film in the course of its flattening. This instability was discovered in 1998 by Debregeas et al. [1] and has been attributed to the joint effect of gravity and the expansion of a circular rupture [2]. However, a recent experiment by Oratis et al. [3] demonstrated that the instability appears even in the absence of gravity or rupture, indicating a mechanism dominated solely by viscous and capillary forces.

Motivated by these experiments we address Stokes flow in a curved film of a non-inertial incompressible liquid with free surfaces, generated by temporal variation of the Gaussian curvature R [4]. Notwithstanding the close analogy between the Newtonian hydrodynamics of viscous liquids and the Hooeakn elasticity of solids, often called “Stokes-Rayleigh analogy”, the fact that stress in viscous films is generated by the rate-of-change ∂tR, rather than by R itself as is the case for elastic sheets, reflects a profound difference between these two branches of non-inertial, yet geometrically-nonlinear continuum mechanics. Whereas the rigidity of elastic sheets derives from the existence of a “target” metric, their viscous counterparts are not endowed with a preferred metric. We reveal the experimental observations of Ref. [3] as a dramatic ramification of this distinction - a universal, curvature-driven & momentum-conserving surface dynamics, imparted by viscous resistance to ∂tR ̸= 0. Specifically, rapidly-depressurized viscous bubbles flatten by forming a radially moving front of highly localized ∂tR that separate a flat core and a spherically-shapes periphery, and become wrinkled due to a hoop-compressive stress field at the wake of the propagating front [5].

This novel surface dynamics has close ties to "Jelium physics", where topological defects spontaneously emerge to screen elastic stress, similarly to dipoles-mediated screening of electrostatic field in conducting media, thereby extending the classic analogy between Wigner crystals, Abrikosov lattice in type-II superconductors, and 2D elasticity of curved crystals, to non-equilibrium 2D viscous hydrodynamics. A particularly exciting possibility is the emergence of such a universal geometrically-noninear 2D viscous hyrodynamics in strongly-correlated electronic liquids in 2D crystals.

[1] G. Debregeas, P.G. de Gennes, F. Brochard-Wyart, "The life and death of 'bare' viscous bubbles," Science 279, 1704-1707 (2000).
[2] R. da Silviera, S.Chaieb, L.Mahadevan, "Rippling instability of a collapsing bubble," Science 287, 1468-1471 (2000).
[3] A.T. Oratis, J.W.M. Bush, H.A. Stone, J. Bird, "A new wrinkle on liquid sheets: Turning the mechanism of viscous bubble collapse upside down," Science 369, 685 (2020).
[4] P.D. Howell, "Models for thin viscous sheets," Eur. J. App. Math. 7, 321-343 (1996).
[5] B. Davidovitch and A. Klein, "How viscous bubbles collapse: topological and symmetry- breaking instabilities in curvature-driven hydrodynamics" (2022).

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Abstract: Buckling of elastic structures is an effective way to produce rapid motion in a fluid at any scale. Encapsulated microbubbles, which are currently used as ultrasound contrast agents, can deform and collapse under an external load from an acoustic wave. They reinflate when the pressure decreases. The shape hysteresis associated with this deformation cycle makes this simple object a good candidate to become an ultrasound controlled micro-swimmer.

I will explore this possibility through experiments at macro and micro scales and numerical simulations. The coupling between the acoustic wave and the self-oscillation of the deformed shell leads to complex - sometimes chaotic - dynamics with direct consequences on the direction and efficiency of the swimming.

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Abstract: The essential role of protein dynamics for enzyme catalysis has become more generally accepted. Since evolution is driven by organismal fitness hence the function of proteins, we are asking the question of how enzymatic efficiency has evolved. First, I will address the evolution of enzyme catalysis in response to one of the most fundamental evolutionary drivers, temperature. Using Ancestral Sequence Reconstruction (ASR), we answer the question of how enzymes coped with an inherent drop in catalytic speed caused as the earth cooled down over 3.5 billion years. Tracing the evolution of enzyme activity and stability from the hot-start towards modern hyperthermophilic, mesophilic and psychrophilic organisms illustrates active pressure versus passive drift in evolution on a molecular level (1). Second, I will share a novel approach to visualize the structures of transition-state ensembles (TSEs), that has been stymied due to their fleeting nature despite their crucial role in dictating the speed of biological processes. We determined the transition-state ensemble in the enzyme adenylate kinase by a synergistic approach between experimental high-pressure NMR relaxation during catalysis and molecular dynamics simulations (2). Third, a novel general method to determine high resolution structures of high-energy states that are often the biologically reactive species will be described (3). With the ultimate goal to apply this new knowledge about energy landscapes in enzyme catalysis for designing better biocatalysts, in “forward evolution” experiments, we discovered how directed evolution reshapes energy landscapes in enzymes to boost catalysis by nine orders of magnitude relative to the best computationally designed biocatalysts. The underlying molecular mechanisms for directed evolution, despite its success, had been illusive, and the general principles discovered here (dynamic properties) open the door for large improvements in rational enzyme design (4). Finally, visions (and success) for putting protein dynamics at the heart of drug design are discussed.

1. V. Nguyen et. al., Evolutionary Drivers of Thermoadaptation in Enzyme Catalysis” Science 2017, 355(6322):289-294
2. J. B. Stiller et. al., Probing the Transition State in Enzyme Catalysis by High-Pressure NMR Dynamics 2019, Nature Catalysis (2019) 2, 726–734
3. J. B. Stiller et. al., Structure Determination of High-Energy States in a Dynamic Protein Ensemble Nature 2022, in press
4. R. Otten et. al., How directed evolution reshapes energy landscapes in enzymes to boost catalysis Science 2020, 2020 Dec 18;370(6523):1442-1446

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Abstract: The collective motion of dense suspensions of swimming bacteria is typical of a broad class of active materials, ranging from flocking birds and schooling fish down to the sub-cellular movement of actin filaments. Descriptions of the dy- namics of these systems have predominately focused on the characterization of spatio-temporal correlations of the velocity field, but whilst the importance of active turbulence is widely recognized, their structure, transport properties and mixing kinematics still remain largely unknown.

Here, we use Lagrangian analysis techniques to study the chaotic flow fields gen- erated by bacterial turbulence in dense suspensions of Bacillus subtilis. High- resolution velocity fields are measured using PIV across a range of bacterial swimming speeds, where the computed Lagrangian stretching visualizes the induced stretching and folding, characteristic of mixing. Close inspection of the finite-time Lyapunov exponent (FTLE) field reveals time and swimming speed dependent FTLE statistics reminiscent of intermittent dynamics in clas- sical chaotic dynamical systems. At moderate P ́eclet numbers, experiments and Langevin simulations reveal that manifolds of the FTLE field guide scalar mix- ing and regulate transport in these active suspensions, ecologically relevant to the dispersal of chemical resources and particulates in dense bacterial colonies.

Secondly, we apply proper orthogonal decomposition (POD) analysis to quantify the dynamical flow structure of active turbulence under a variety of conditions. In isotropic bulk turbulence, the modal representation shows that the most en- ergetic flow structures dictate the spatio-temporal dynamics across a range of suspension activity levels. In confined geometries, POD analysis illustrates the role of boundary interactions for the transition to bacterial turbulence, and it quantifies the evolution of coherent active structures in externally applied flows. Beyond establishing the physical flow structures underpinning the complex dy- namics of bacterial turbulence, the low-dimensional representation afforded by this modal analysis will facilitate data-driven modeling of active turbulence.

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Since its inception in 2004, the Microbial Science Initiative has sponsored and hosted an annual symposium for those in the Harvard and greater Boston communities. The spring event showcases magnificent research across a breadth of microbe-centric topics spanning environmental and biomedical sciences. The MSI Symposium is free and open to the public. Welcome to the microbial world! Mid-morning and mid-afternoon breaks with refreshments will be provided, and there will be a 75 minute break for lunch mid-day.

Abstract: Active matter describes out-of-equilibrium materials composed of motile building blocks that convert free energy into mechanical work. The continuous input of energy at the particle scale liberates these systems from the constraints of thermodynamic equilibrium, leading to emergent collective behaviors not found in passive materials. In this talk, I will describe our recent efforts to build simple active systems composed of purified proteins and identify generic emergent behaviors in active systems. I will first discuss two distinct activity-driven instabilities in suspensions of microtubules and molecular motors. Second, I will describe a new model system for polar fluid whose collective dynamics are driven by the non-equilibrium turnover of actin filaments. Our results illustrate how biomimetic materials can serve as a platform for studying non-equilibrium statistical mechanics, as well as shine light on the physical mechanisms that regulate self-organization in living matter.

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Abstract: Active-matter physics describes the mesmerizing dynamics of interacting motile bodies : from bird flocks and cell colonies, to collections of synthetic units independently driven far from equilibrium. When motile units self-assemble into flocks where all particles propel along the same direction, they realize one of the most robust ordered phase observed in Nature. But, after twenty five years of intense research the very mechanism controlling the ordering dynamics of both living and artificial flocks has remained unsettled.

In this talk, building on model experiments based on Quincke rollers, I will first explain how a flock suppresses its singularities to form an ordered spontaneous flow. Combining experiments, simulations and theory I will show how to elucidate the elementary excitations of 2D polar active matter and explain their phase ordering dynamics as a self-similar process emerging from the annihilation of ±1 defects along a filamentous network of domain walls with no counterparts in passive systems.

In a second part, I will address the robustness of long range order and discuss the stabilization of topological defects in a polar active fluid through disordered media. Combining experiments and theory, I will show that colloidal flocks collectively cruise through disorder without relaxing the topological singularities of their flows, unlike in pure systems. Introducing colloidal flocks in micro patterned circular chambers, we reveal a state of strongly disordered active matter with no counterparts in equilibrium : a dynamical vortex glass. The resulting state is highly dynamical but the flow patterns, shaped by a finite density of frozen vortices, are stationary and exponentially degenerated.

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Abstract: Living organisms rely on flows to perform essential functions that range from swimming and feeding in unicellular organisms to mucus clearance in humans. These flows are generated by the inte­grated activity of thousands of microscopic beating filaments attached to cell surfaces (cilia). In cells, collections of cilia exhibit highly complex temporal patterns known as metachronal waves. The lack of measurements of the geometric and dynamic properties of cilia arrays has limited our ability to understand the mechanisms of pattern formation. In my talk I will discuss the advantages of ciliated swimmers as experimental model systems where such measurements can be readily performed. Performing precise measurements and perturbations of temporal patterning in cilia arrays will enable the identification of the physical mechanisms underlying collective behaviors of cilia. This integrated view that seeks to link cilia patterning with flow structure will significantly increase our understanding of the physiology of cilia arrays in vivo.

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Abstract: The morphogenesis of branched tissues has been a subject of long-standing debate. Although much is known about the molecular pathways that control cell fate decisions, it remains unclear how macroscopic features of branched organs, including their size, network topology and spatial pattern are encoded. Based on large-scale reconstructions of the mouse mammary gland and kidney, we begin by showing that statistical features of the developing branched epithelium can be explained quantitatively by a local self-organizing principle based on a branching and annihilating random walk (BARW). In this model, renewing tip-localized progenitors drive a serial process of ductal elongation and stochastic tip bifurcation that terminates when active tips encounter maturing ducts. Then, based on reconstructions of the developing mouse salivary gland, we propose a generalisation of BARW model in which tips arrested through steric interaction with proximate ducts reactivate their branching programme as constraints become alleviated through the expansion of the underlying mesenchyme. This inflationary branching-arresting random walk model offers a more general paradigm for branching morphogenesis when the ductal epithelium grows cooperatively with the tissue into which it expands.

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Abstract: The out-of-equilibrium active reorganization of cytoskeletal networks by molecular motors is necessary for fundamental life processes, such as cell division, cell motility, and environmental sensing. While the passive structure and mechanics of such materials have been well documented, the effects of their steady-state out-of-equilibrium reorganization is a site of current research. In this work, we introduce an active cytoskeletal composite material whose viscoelasticity is controlled by the actin filament concentration. Three qualitatively different states are observed: (1) an extensile fluid phase, (2) localized aster-like contractile structures in coexistence with an extensile fluid, and (3) a bulk contractile gel. The aster-like state consists of locally contracted heterogeneous structures that maintain their complex layered structure over a range of sizes. While the actin concentration triggers a contractile state in coexistence with the active fluid, the resultant filament-rich structures are transient and their lifetimes increase with actin concentration. These results demonstrate that self-organized dynamical states and patterns, evocative of those observed in the cytoskeleton, do not require precise biochemical regulation but can arise due to purely mechanical interactions of actively driven filamentous materials.

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Abstract: Meiosis is the specialized form of cell division in which gametes are created. In meiosis, a mother cell must ensure that the daughter gamete inherits exactly one copy of each chromosome. This, in turn, necessitates physical organization and motion of DNA over length scales of tens of microns. To create the forces required to move chromosomes, the cell builds an organelle called the meiotic spindle. Like the analogous structure in mitotic cells, the meiotic spindle is composed primarily of microtubules -- long, rigid protein polymers -- as well as a variety of other proteins. Some of these associated proteins create (active or passive) forces between microtubules; another class allows microtubules to exert forces on chromosomes.

Despite our detailed knowledge of the spindle's molecular composition, as mechanical objects, both meiotic and mitotic spindles are very poorly understood. It is not known, for instance, which specific molecular or structural components of the spindle are responsible for generating the forces that actually move chromosomes, or which components transfer those forces to chromosomes. Likewise, from a materials physics perspective, it is unclear how we should think about self-organized, biochemically complex, fuel-consuming structures like the spindle.

In this talk, I will discuss how we can adapt a variety of tools from materials physics to characterize various aspects of the spindle's microscopic structure and organelle-scale physical properties, like elastic stiffness and surface tension. I will discuss our attempts to understand these measurements within the context of a quantitative, coarse-grained theory in which spindles from mouse and human eggs are modeled as active liquid crystal droplets.

More about the Squishy Physics Seminar

Abstract: The human gut microbiome is highly temporally dynamic. Some of the most profound changes over time occur during infancy and early childhood when the microbiome is first becoming established. Although the gut microbiome is more stable in adulthood, it continues to undergo significant changes over time due to diet, travel, antibiotic use, infection, gut inflammation, and a variety of other factors. Microbial dynamics, particularly early in life, have been linked to many human diseases including necrotizing enterocolitis, diabetes, food allergies, obesity, and inflammatory bowel diseases. Given the complexity of complex and dynamic host-microbial ecosystems, sophisticated computational methods are essential for analyzing data from these systems and ultimately deriving experimentally testable hypotheses. In this talk, I will first introduce the challenges of analyzing dynamic microbiomes. Then, I will present intuitive descriptions of some of the novel machine learning methods we have developed to address different problems, including: (a) forecasting microbiome dynamics and quantitating the “keystoneness” of individual microbes or groups of microbes, (b) finding groups of microbes that respond consistently to introduced perturbations, and (c) predicting the status of the human host (e.g., disease onset) given past changes in the microbiome. Throughout, I will give examples of biomedical applications of our work, including developing microbial consortia to treat or prevent Clostridioides difficile infection or food allergies. I will gear the talk to a broad audience, focusing on the intuition behind machine learning approaches rather than technical details.

Register for (remote only) MSI Thursday Seminar Series

Abstract: Hydrogels that provide mechanical support and sustainably release therapeutics have been used to treat tendon injuries. However, most hydrogels are insufficiently tough, release drugs in bursts, and require cell infiltration or suturing to integrate with surrounding tissue. Here we report that a hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a chitosan adhesive surface on the other side supports tendon gliding and strong adhesion (larger than 1,000 J m-2) to tendon on opposite surfaces of the hydrogel, as we show with porcine and human tendon preparations during cyclic-friction loadings. The hydrogel is biocompatible, strongly adheres to patellar, supraspinatus and Achilles tendons of live rats, boosted healing and reduced scar formation in a rat model of Achilles-tendon rupture, and sustainably released the corticosteroid triamcinolone acetonide in a rat model of patellar tendon injury, reducing inflammation, modulating chemokine secretion, recruiting tendon stem and progenitor cells, and promoting macrophage polarization to the M2 phenotype. Hydrogels with 'Janus' surfaces and sustained-drug-release functionality could be designed for a range of biomedical applications.

More about the Squishy Physics Seminar

Abstract: The developmental cycle of Myxococcus xanthus involves the coordination of many hundreds of thousands of cells aggregating to form mounds known as fruiting bodies. This aggregation process begins with the sequential formation of more and more cell layers. Using three-dimensional confocal imaging we study this layer formation process by observing the formation of holes and second layers within a base monolayer of M xanthus cells. We find that cells align with each other over the majority of the monolayer forming an active nematic liquid crystal with defect point where cell alignment is undefined. We find that new layers and holes form at positive and negative topological defects respectively. We model the cell layer using hydrodynamic modeling and find that this layer and hole formation process is driven by active nematic forces through cell motility and anisotropic substrate friction.

More about the Active Matter Seminar

Abstract: Biological responses to biomaterials are a complex topic as they not only involve diverse bio-components (such as proteins, cells, blood, etc.) but also sophisticated materials with a large array of relevant properties. As our understanding of structure-property–function relationships grows, it is becoming clear that a slight change of a single material property can heavily affect biological responses and many factors remain unknown about these relationships. For example, TiO2 nanotubes (TNTs) have a similar structure to the natural compact bone, and studies have confirmed TNTs can improve osteogenic differentiation. However, the structural properties of titanium dioxide nanotubes are diverse, and the optimal TNTs for bone repair remain to be determined. In this talk, I will discuss how the surface properties of TiO2 nanomaterials affect the biological response, including protein adsorption, cell behaviors and platelet adhesion. Our results show that the various structural properties of these material surfaces do not vary individually and will synergistically affect biological responses. On the other hand, we can obtain different or even opposite results by tuning experimental details.

More about the Squishy Physics Seminar

Abstract: Coarse-Graining (CG) is a simulation strategy that simplifies all-atom molecular systems by grouping selected atoms into pseudo-beads and propagating their motion collectively. CG drastically accelerates simulations for two reasons: first there are fewer particles to simulate and second the dynamics can be integrated with larger time steps.

Coarse-graining involves two coupled learning problems: defining the mapping from an all-atom representation to a reduced representation, and parameterizing a Hamiltonian over coarse-grained coordinates. We have recently proposed a generative modeling framework based on variational auto-encoders to unify the tasks of learning discrete coarse-grained variables and parameterizing coarse-grained force fields. Furthermore, CG approaches result in irreversible information loss, which makes accurate backmapping, i.e., restoring fine-grained (FG) coordinates from CG coordinates, a long-standing challenge. We propose a model that rigorously embeds the probabilistic nature and geometric consistency requirements of the backmapping transformation. The model encodes the distribution of FG expansions of the beads into an invariant latent space and decodes them back to FG geometries via equivariant convolutions.

Abstract: The spontaneous emergence of collective flows is a generic property of active fluids and often leads to chaotic flow patterns characterized by swirls, jets, and topological disclinations in their orientation field. I will first discuss two examples of these collective features helping us understand biological processes: (i) to explain the tortoise & hare story in bacterial competition: how motility of Pseudomonas aeruginosa bacteria leads to a slower invasion of bacteria colonies, which are individually faster, and (ii) how self-propelled defects lead to finding an unanticipated mechanism for cell death.

I will then discuss various strategies to tame, otherwise chaotic, active flows, showing how hydrodynamic screening of active flows can act as a robust way of controlling and guiding active particles into dynamically ordered coherent structures. I will also explain how combining hydrodynamics with topological constraints can lead to further control of exotic morphologies of active shells.

More about the Active Matter Seminar

Abstract: Suspensions of microscopic particles, such as reaction mixtures with catalyst particles and nutrient solutions with bacteria, often contain heterogeneous distributions of solute. The concentration gradients that result from these inhomogeneities can put the particles in motion through a process called phoresis, or chemotaxis in the case of living systems. Through this process bacteria manage to find places with higher nutrient concentrations and white blood cells can chase after bacteria. In this work, we employed a model system of oil droplets that exchange oil with each other in an aqueous surfactant solution to study the forces that particles exert on each other through the formation of local concentration gradients. We found that the solute-mediated interactions can be repulsive or attractive depending on the rate of oil exchange. When the type of oil droplets and surfactant are chosen correctly, one type of droplet chases after the other.

Abstract: Cells sense and respond to their physical surroundings using organized molecular machinery that is tightly regulated in space and time. Although each of us feels like an individual we are, in fact, consortia. This becomes clear when we observe tissues under the microscope, but very little is known how the material properties of these tissues emerged from a vast majority of life forms that employ rigid cell walls to withhold their turgor pressure. Here, I will discuss how multicellularity first emerged in archaeal cells - the closest prokaryotes to animals. We observed that not only multiple lineages of archaea create multicellular colonies, but also that physical compression triggers a developmental program in some species cells that leads to a multicellular physiological state. We show this new mechanosensing mechanism is independent of the stiffness or rugosity of the surfaces around cells and there are specific molecular sensors that allow cells to sense the viscoelasticity state of their envelope. Altogether, our data suggest archaea should be an interesting model for the development of bioinspired material and the study of how physical constraints shape evolution.

Abstract: My lab is interested in the active and adaptive materials that underlie control of cell shape. This has centered around understanding force transmission and sensing within the actin cytoskeleton. I will first review our current understanding of the types of active matter that can be constructed by actin polymers. I will then turn to our recent experiments to understand how Cell shape changes in epithelial tissue. I will describe the two sources of active stresses within these tissues, one driven by the cell cycle and controlling cell-cell stresses and the other controlled by cell-matrix signaling controlling motility. I will then briefly describe how we are using optogenetics to locally control active stresses to reveal adaptive and force-sensitive mechanics of the cytoskeletal machinery. Hopefully, I will convince you that recent experimental and theoretical advances make this a very promising time to study this quite complicated form of active matter.

More about the Active Matter Seminar

Abstract: Collectively migrating cells in living organisms often take advantage of barriers and internal interfaces to achieve directed motion, although the physical origin of this behavior is still debated. Here we demonstrate that human fibrosarcoma cells (HT1080) plated on narrow stripe-shaped channel undergo collective migration by virtue of a novel type of topological edge currents, resulting from the interplay between liquid crystalline (nematic) order, microscopic chirality and topological defects. Thanks to a combination of in vitro experiments and theoretical active hydrodynamics, we show that, while heterogeneous and chaotic in the bulk of the channel, the spontaneous flow arising in confined populations of HT1080 cells is rectified along the edges, leading to directed motion, with broken parity symmetry. These edge currents are fueled by layers of +1/2 topological defects, anchored at approximately 74 degrees with respect to the channel's edge and acting as local sources of chiral active stress. This shows how multicellular systems can take advantage of topology to achieve collective migration, even in the absence of hard-wall confinement. Finally, it demonstrates the importance of chirality in these systems and suggests a possible mechanism for the emergence of chiral cellular flows in vivo.

Abstract: Cell membrane remodeling is involved in many important cellular events such as cell division and virus infection. Multiple possible mechanisms for membrane remodeling have been proposed over the years, ranging from intuitive factors such as shallow insertion of protein motifs to more recent discovery of contributions from collective processes such as liquid-liquid phase separation of prepheral proteins. To help establish the relative importance of various factors to the specific system of interest, including the effect of disease-causing mutations, it is desirable to develop multi-scale models that are sensitive to molecular details, such as protein sequence and membrane composition, yet computationally efficient for studying the process of membrane remodeling. Using several examples from our recent studies, which involve protein and nanoparticle regulated membrane remodeling, we highlight both challenges and progress made in developing such multi-scale computational models, and initial mechanistic insights into ESCRTIII driven membrane fission. Finally, we will also briefly discuss the potential involvement of pre-wetting transitions at membrane surface as a mechanism that disordered proteins drive membrane remodeling, including the impact of membrane obstacles (e.g., proteins anchored to cytoskeletons) on the sensitivity of such a mechanism.

Abstract: Fluids pervade complex systems, ranging from fish schools, to bacterial colonies and nanoparticles in drug delivery. Despite its importance, little is known about the role of fluid mechanics in such applications. Is schooling the result of vortex dynamics synthesized by individual fish wakes or the result of behavioral traits? Is fish schooling energetically favorable? I will present multifidelity computational studies of collective swimming in 2D and 3D flows. Our studies demonstrate that classical models of collective swimming (like the Reynolds model) fail to maintain coherence in the presence of long-range hydrodynamic interactions. We demonstrate in turn that collective swimming can be achieved through reinforcement learning. We extend these studies to 2D and 3D viscous flows governed by the Navier Stokes equations. We examine various hydrodynamic benefits with a progressive increase of the school size and demonstrate the importance of controlling the vorticity field generated by up to 300 synchronized swimmers.

More about the Active Matter Seminar

Abstract: Water is essential for all forms of life. However, some organisms survive severe desiccation by undergoing cryptobiosis, during which most metabolic processes are suspended and the host organism enters a dormant, protective state until a favorable environment is restored. Recent studies have demonstrated that intrinsically disordered proteins (IDPs) are often expressed at high levels in extremotolerant tardigrades, suggesting that this class of unstructured protein is critical to maintaining cell survival under adverse conditions. We focus on specific class of tardigrade-specific IDPs that are secreted extracellularly, characterize their structures and phase separation behaviors, and investigate protective phenotypes both in vitro and in vivo. Ultimately, we hope to explore applications of these proteins in engineering drought tolerance in mammalian cells, or stabilizing biomedical products for long-term storage.

Abstract: Integrating synthetic circuitry into larger transcriptional networks to mediate predictable cellular behaviors remains a challenge within synthetic biology. While significant efforts have been devoted to the design of enhanced synthetic circuitry, less is understood regarding how cellular hardware may impose fundamental performance limitations on integrated circuits. Within the mammalian context, cellular reprogramming continues to generate new cell types, increasingly expanding our perspective of cellular plasticity. Despite improved genetic tools and epigenetic modulations, reprogramming remains a rare cellular event. In this talk, I will describe how we identified molecular roadblocks in reprogramming that arise from tradeoffs between transcription and proliferation rates. Our discovery suggests that topological stress impacts the function of gene networks and constrains cellular transitions. To test this hypothesis, my lab constructs synthetic gene circuits that transmit topological stress into changes in expression to identify plastic cells in cell-fate transitions through the model of cellular reprogramming. I will discuss how this work and recent findings from my lab open completely new questions about how the structure of the genome stabilizes cellular identity and suggests strategies to improve the design of synthetic gene circuits.

Abstract: Experiments with fire-ant columns reveal similarities and differences with granular columns. There are force chains, but these are always supportive (not compressive) and fluctuate due to activity. In 2D columns, we observe the propagation of waves along the vertical direction; these are density, activity and alignment waves, ultimately reflecting the existence of activity cycles whereby the fire-ant collective changes “state” from “active”, where all the ants move, to “inactive”, where a large fraction of the ants cluster and remain stationary. Our findings indicate that while the “active” states correspond to collective motion, in the “inactive” states there is clustering reminiscent of a motility-induced attraction resulting from the social interactions between the ants.

Abstract: The mammalian sensory nervous system densely innervates barrier tissues including the skin and gut that are exposed to microbes. Nociceptors are specialized neurons that mediate pain and itch. These unpleasant sensations are critical to protect organisms from danger. We find that nociceptors actively participate in host defense by detecting bacterial pathogens and signaling to the immune system. We will explore how bacteria interact with neurons to drive pain and itch, and how this crosstalk could regulate host defense.

Watch "Bacterial Interactions with Pain and Itch" on YouTube

Abstract: If a sessile droplet containing suspended particulates evaporates on a substrate, it eventually leaves a ring pattern due to non-uniform evaporative flux profiles. To control and suppress coffee-ring effects, it is important to understand how the flow structures evolve and what kind of solvent and solute components are. We use solutal Marangoni stresses and geometrical effects to control the dried pattern. In this talk, I will present a series of representative examples of how to control or suppress the coffee-ring pattern and furthermore new features will be identified and exploited. The examples include that (1) whisky dried patterns, (2) DNA droplet, (3) coffee-ring-less QD-LED polygonal patterns, and (4) liquid metal coating and its applications. These problems characterize my approach of using optical measurement techniques to explore new questions in multiphase flows and physicochemical hydrodynamics.

Wylie Dufresne (@WylieDufresne), Du's Donuts & Coffee, BK, Stretch Pizza (formerly wd~50)
Ted Russin (@CIACulinarySci) School of Culinary Science and Nutrition, Culinary Institute of America

Abstract: Generating neutralizing antibodies (Abs) is one of the key functions of vaccines. These high affinity Abs bind to active sites of proteins on pathogens' surfaces, prevent their entry into host cells, and mark them for elimination via innate immune cells. While vaccines are intended to elicit such protection, some fail to induce neutralizing Abs against diseases such as HIV. To understand this variability, we must look to the germinal centers (GCs) within follicles, where B-cells interact with both the vaccine antigen (Ag) and T-cells as they mutate their receptors during affinity maturation. Recent studies illustrate that large proportions of GC B-cells do not recognize intact vaccine Ags and lead to formation of plasma cells that secrete Abs incapable of neutralizing the actual virus. This prompted us to evaluate the stability of Ags in vivo and examine the protease activity within LNs after immunization; areas that are both severely understudied in vaccinology. By developing dye labeled HIV Ags that show a loss in fluorescence resonance energy transfer (FRET) with degradation, we discovered regions of intact and degraded Ags within the LNs. This was caused by a class of functionally active proteases that are upregulated in a spatially dependent manner and are expressed within cells that come into direct contact with the lymph-borne Ags. To examine the impact of Ag proteolysis, we used different vaccination conditions that show spatially distinct localization of Ag within LNs and investigated the capacity of the corresponding GC and Ab responses to recognize intact Ags or degraded Ag by-products. Our work here illuminates the role of protease activity within LNs shortly after vaccination and its role in modulating downstream humoral response.

Abstract: Understanding how organs transform into their target shapes during development is a challenge at the interface between physics and biology. In visceral organs, multiple tissue layers interact to orchestrate complex shape changes. While there has been significant progress in identifying genetic and anatomical ingredients underlying organogenesis, tracing the dynamics of cell behavior and tissue deformation that drive organ shape change remains an outstanding and essential challenge. Here, leveraging the Drosophila midgut as a model system, we use light-sheet microscopy, optogenetics, computer vision, and tissue cartography to reconstruct in toto shape dynamics of a developing organ in vivo. We identify the kinematic and biological mechanisms driving shape change by linking out-of-plane motion to active contraction patterns cell behaviors, and genetic patterning. Our multi-scale analysis traces how biology controls a physical process generating whole-organ shape change in heterologous tissue layers.

Abstract: Control over the fate of excited states at the nanoscale is the holy grail of excitonic devices, including light-emitting diodes and photovoltaic devices. Photosynthesis provides the master blueprint on how we can move energy efficiently through molecules. However, dissecting the salient parts that underlie this efficient steering of energy is encumbered by challenges in re-engineering natural machines without losing function. Alternative to re-engineering photosynthetic machinery, we have recently developed a bottom-up approach using DNA to emulate the chromophore organization in nature light-harvesting systems. DNA provides a rich molecular toolbox to control the spatial relationships of multiple synthetic pigments enabling us to recapitulate emergent quantum behavior of molecular aggregates found in photosynthetic machines. In this talk, I'll discuss our recent work on DNA templated aggregates, how we can use DNA to form aggregates with defined electronic structures, and the function of these aggregates in the context of energy transport. Finally, I'll show some ongoing work in the lab that seeks to understand the complex interplay between long-range, Coulombic, and short-range, charge-transfer interactions.

Dr. Maya Warren (@maya.warren), Ice Cream Scientist

Watch "The Science of Ice Cream" on YouTube

Abstract: Innovation in food science and technology is the alternative to overcome the current challenges of the food industry. In my talk, I will discuss some food model systems that we are currently exploring through knowledge/tools from chemistry, biology, and physics. For example, despite goat milk having benefits for human health over cow's milk, goat milk yogurt (GY) has a delicate texture, a more rupture-susceptible gel structure, low consistency, and viscosity, which reduces its overall acceptability by the consumer. Thus, new innovative methods such as ultrasound and high hydrostatic pressure can be alternatives to improve the quality of GY. Furthermore, the addition of inulin, maltodextrin, whey protein, and cupuassu pulp can improve the taste and rheological characteristics of goat milk yogurts. Recent advances on kefiran, an exopolysaccharide derived from kefir grain microflora, have shown its electrospinning ability to be transformed in nanofiber, potentially useful for encapsulating bioactive ingredients for food, probiotic/ drug delivery, and scaffolds to tissue engineering. On the other hand, conventional food preservation methods have demonstrated several disadvantages and limitations in the efficiency of microbial load reduction and maintaining food quality. Hence, non-thermal preservation technologies (NTPT) and alternative chemical compounds (ACC) have been considered a high promising replacer for decontamination, increasing the shelf life and promoting low levels of physicochemical, nutritional, and sensorial alterations in meat and fish. However, NTPT promotes the connections between the oxidative process (lipids and proteins) and the impact of color and rheology characteristics. The demand for more environment-friendly technologies has gained worldwide attention to food processing and preservation. Brazil has over 40,000 varied plant species rich in phytochemicals, which have great potential as a source of ACC that can be replacer for synthetic compounds currently applied in the meat industry. Nevertheless, natural antioxidant compounds are not stable. In this way, nanocomposites based on biodegradable polymer/graphene-based nanomaterials with antioxidant activity can be combined with natural antioxidants and applied in the meat industry. I will also share some of our recent data that shows how the science behind food processing and preservation can be interesting and beneficial to the food industry, consumers and government.

Alexandra Whisnant (@gatecommedesfilles), chocolatier, gâté comme des filles, Somerville, MA

Abstract: Innovation in food science and technology is the alternative to overcome the current challenges of the food industry. In my talk, I will discuss some food model systems that we are currently exploring through knowledge/tools from chemistry, biology, and physics. For example, despite goat milk having benefits for human health over cow's milk, goat milk yogurt (GY) has a delicate texture, a more rupture-susceptible gel structure, low consistency, and viscosity, which reduces its overall acceptability by the consumer. Thus, new innovative methods such as ultrasound and high hydrostatic pressure can be alternatives to improve the quality of GY. Furthermore, the addition of inulin, maltodextrin, whey protein, and cupuassu pulp can improve the taste and rheological characteristics of goat milk yogurts. Recent advances on kefiran, an exopolysaccharide derived from kefir grain microflora, have shown its electrospinning ability to be transformed in nanofiber, potentially useful for encapsulating bioactive ingredients for food, probiotic/ drug delivery, and scaffolds to tissue engineering. On the other hand, conventional food preservation methods have demonstrated several disadvantages and limitations in the efficiency of microbial load reduction and maintaining food quality. Hence, non-thermal preservation technologies (NTPT) and alternative chemical compounds (ACC) have been considered a high promising replacer for decontamination, increasing the shelf life and promoting low levels of physicochemical, nutritional, and sensorial alterations in meat and fish. However, NTPT promotes the connections between the oxidative process (lipids and proteins) and the impact of color and rheology characteristics. The demand for more environment-friendly technologies has gained worldwide attention to food processing and preservation. Brazil has over 40,000 varied plant species rich in phytochemicals, which have great potential as a source of ACC that can be replacer for synthetic compounds currently applied in the meat industry. Nevertheless, natural antioxidant compounds are not stable. In this way, nanocomposites based on biodegradable polymer/graphene-based nanomaterials with antioxidant activity can be combined with natural antioxidants and applied in the meat industry. I will also share some of our recent data that shows how the science behind food processing and preservation can be interesting and beneficial to the food industry, consumers and government.

Abstract: Living matter relies on the self organization of its components into higher order structures, on the molecular as well as on the cellular, organ or even organism scale. Collective motion due to active transport processes has been shown to be a promising route for attributing fascinating order formation processes on these different length scales. Here I will present recent results on structure formation on actively transported actin filaments on lipid membranes and vesicles, as well as the cell migration induced structure formation in the developmental phase of pancreas organoids.

Bryan Furman (@bs_pitmaster), Pitmaster, Bryan Furman BBQ, B's Cracklin Barbecue, Chef in Residence at Stone Barns Center for Food & Agriculture

Amanda Cohen (@dirtcandynyc), Dirt Candy, New York, NY

Tracy Chang (@gopagu), Pagu Restaurant, Cambridge, MA

Watch "The Science of Hand Pulled Noodles" on YouTube

Jason White (@teamsilent), Director of Fermentation at NOMA, Copenhagen, Denmark

Watch "Fermentation: A Springboard for Modern Gastronomy" on YouTube

Joanne Chang '91 (@jbchang), Flour Bakery and Café, Myers + Chang, author of "Flour", "Flour Too", "Myers + Chang at Home", and "Baking With Less Sugar"

Watch "The Science of Sugar" on YouTube

Dave Arnold (@cookingissues), Booker and Dax, author of "Liquid Intelligence," host of "Cooking Issues," founder of the Museum of Food and Drink

Harold McGee (@mcgee.onfood.onsmells), author of "On Food and Cooking," "Curious Cook," "Nose Dive: A Field Guide to the World's Smells"

Guillaume Duclos, Brandeis University
  Instabilities and liquid to solid transition in a three-dimensional active network
Margaret Gardel, University of Chicago
  Building soft, living materials
Mathias Kolle, MIT
  Optical emulsions, focused and in color
Chinedum Osuji, University of Pennsylvania
  Block Copolymer Assembly Nematic Solvents

Katy Rothenberg
11am - noon | Remote meeting
Attend Cell Migration Seminar

Mohit Kumar Jolly
11am - noon | Remote meeting
Attend Cell Migration Seminar

I present a new mechanism whereby spatially varying order in a thin liquid crystal film, induced by chemical or topographic patterning on a substrate, can lead to spontaneous topography on an opposing free interface. Analytical and numerical results will be shown to elucidate this mechanism, together with recent experimental evidence and connections to other free interface problems.

Jude Phillip
11am - noon | Remote meeting
Shashank Shekhar
11am - noon | Remote meeting
Multicomponent molecular mechanisms of actin dynamics regulation in motile cells Attend Cell Migration Seminar

Robert Fischer
11am - noon | Remote meeting
Riding the wave: how ECM waves can depolarize cancer cells
Isabelle Caille
11am - noon | Remote meeting
Primary cilium-dependent cAMP/PKA signalling at the centrosome regulates neuronal migration Attend Cell Migration Seminar

Spoorthi Subramaniam
11am - noon | Remote meeting
Guidance mechanisms involved in melanocyte patterning and survival Jorg Renkawitz
11am - noon | Remote meeting
Leukocyte navigation in 3D microenvironments Attend Cell Migration Seminar

Abstract: Open any biology textbook and you are likely to learn that, in contrast to eukaryotes, bacteria do not contain organelles to compartmentalize and facilitate cellular functions. However, numerous protein- and lipid-bounded organelles are known to exist within a diverse array of bacterial species. In my group, we look at the process of compartmentalization at a molecular level in order to understand the origins and functions of bacterial organelles and exploit them for future applications. I will discuss our work on the biogenesis and subcellular organization of the magnetic magnetosome organelles of magnetotactic bacteria and our recent discovery of ferrosomes—iron-accumulating compartments that define a novel class of bacterial organelles.

Watch "The ins and outs of bacterial organelles" on YouTube

Self-assembly of simple subunits into multi-subunit structures with increased complexity and functionality underlies many biological processes and is becoming an important route to bottom-up materials design. In this talk I will consider a special class of self-assembly processes --- self-limiting assembly --- defined as an assembly process that autonomously terminates at an equilibrium structure with a well-defined, finite size that is much larger than the size of individual subunits. I will begin with an overview of the basic statistical mechanical framework that describes the thermodynamics of self-assembly. With this framework, I will introduce the physical ingredients that are required to achieve self-limited assembly. I will then discuss three (time permitting) examples of self-limiting assembly, with results from theoretical and computational modeling as well as from experiments by collaborators: (1) Bacterial microcompartments, which are ‘organelles' inside of bacteria, consisting of large icosahedral protein shells that assemble around collections of enzymes; (2) Synthetic capsids (icosahedral shells) formed by self-assembling DNA origami subunits; and (3) Tubules whose self-assembly terminates at a well-defined length due to geometric frustration.

Eva Crosas Molist
11am - noon | Remote meeting
AMPK is a mechano-metabolic sensor linking mitochondrial dynamics to Myosin II dependent cell migration Vicky Sans Moreno
11am - noon | Remote meeting
The actomyosin cytoskeleton in cancer: cell migration and beyond

First, I'll present triaxial weaving, a craft technique used to generate surfaces using tri-directional arrays of initially straight elastic ribbons. We achieve smooth, three-dimensional weaved structures by prescribing in-plane curvatures to the flat ribbons. The potential of this novel design scheme is demonstrated with a few canonical target shapes.

Second, I'll present the mechanics of two elastic rods in a crossing contact, whose geometric counterpart is often referred to in the mathematics community as a ‘clasp.' We compare our experimental and computational results to a well-established description for ideal clasps of geometrically rigid strings, finding that the latter acts as an underlying ‘backbone' for the full elasticity solution.

Samantha Payne
11am - noon | Remote meeting
Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance Madeleine Oudin
11am - noon | Remote meeting

Vera Belyaeva
4 - 5pm | Remote meeting
Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance Marcus Bischoff
11am - noon | Remote meeting
Coordination of cytoskeletal dynamics during the transition from migration to apical constriction during Drosophila abdominal morphogenesis

Abstract: The spreading dynamics of genetic information plays a key role in evolution of spatially structured populations. Diffusive populations (which experience short-ranged migration or dispersal behaviour) exhibit spatiotemporal patterns of genetic variation which differ markedly from well-mixed populations (where each individual interacts with all others over the population range). Between these two extremes lies the situation of populations experiencing long-range dispersal, with migration events drawn at random from a broad probability distribution (akin to Lévy flights). Although long-range dispersal is ubiquitous in nature (plants whose seeds and pollen are spread wide by wind, water, or animals; pathogens riding on jetsetting humans), its evolutionary consequences are still being uncovered. I'll talk about recent work that uses simulations and theory to elucidate the patterns left behind by multiple genetic variants during range expansions driven by stochastic long-range dispersal. By studying a class of models in which the dispersal distribution is systematically broadened, I'll show how stochastic effects accumulate to give rise to qualitatively different phases and counterintuitive effects on both local and population-wide genetic diversity.

Abstract: Phase separation is a common theme in physical and biological contexts, including the demixing of unlike lipids in cell membranes, the formation of membraneless compartments in the cytoplasm of cells, and the separation of cooled metal alloys. Although the equilibrium nature of such phase separations is now well-established, textbook material, new and surprising phenomena occur when such systems are driven out of equilibrium. I will describe the formation of striped phases in models of phase separating, binary mixtures under an applied field which drives the mixture in one direction. The drive induces a stripe order with the stripe size decreasing with increasing drive. Signatures of this stripe order persist in the disordered (mixed) phase and generate characteristic peaks in the structure factor of the mixture, reminiscent of an equilibrium microemulsion phase. I will then discuss the prospects of understanding this phenomenon more generally by deriving a coarse-grained field theory for the driven mixture.

Abstract: Topological defects are fundamental to the chaotic self-stirring dynamics of active nematics: materials with liquid crystal-like order but also a continual generation of non-equilibrium internal forces. In 2D active nematic monolayers, point-like disclination defects continually unbind, self-propel, and annihilate in pairs of opposite winding number. This generic behavior has recently been identified in a broad range of biophysical systems including growing bacterial colonies and epithelial tissues. However, bulk active materials cannot behave in the same way, because nematic defects are much more complex in 3D. Here, I'll show that the predominant topological excitations of 3D active nematics are closed-loop disclination lines that change type along their length and are topologically neutral as a whole—that is, they arise individually and self-annihilate. I'll also explore other uniquely 3D phenomena seen in active nematics, including twist distortions, defect reconnections, and a self-reconfiguring network of extended disclination lines.

Abstract: The ability of a material to undergo limited deformation is a critical aspect of conferring toughness as this feature enables the local dissipation of high stresses, which would otherwise cause fracture. The mechanisms of such deformation can be widely diverse. Although plasticity from dislocation motion in crystalline materials is most documented, inelastic deformation can also occur via in situ phase transformations in certain metals and ceramics, sliding of mineralized collagen fibrils in rooth dentin and bone, rotation of such fibrils in skin, frictional motion between mineral "platelets" in seashells, and even by mechanisms that also lead to fracture such as shear banding in glasses and microcracking in geological materials and bone. Resistance to francture (toughness) is thus a compromise—a combination of two, often mutually exclusive, properties of strength and deformability. It can also be considered as a mutual competition between intrinsic damage processes that operate ahead of the tip of a crack to promote its advance and extrinsic crack-tip shielding mechanisms that act mostly behind the crack tip to locally diminish crack-tip stresses and strains. Here we examine the interplay between strength and ductility and between intrinsic and extrinsic mechanisms in developing toughness in a range of biological and natural materials, including bone, skin and fish scales, and in new advance metallic alloys, notably high-entropy alloys.
YouTube recorded Webinar

Abstract: The interplay between fluid flows and living organisms plays a major role in the competition and organization of microbial populations in liquid environments. Hydrodynamic transport leads to the dispersion, segregation or clustering of biological organisms in a wide variety of settings. To explore such questions, we have created microbial range expansions in a laboratory setting by inoculating two identical strains of S. cerevisiae (Baker's yeast) with different fluorescent labels on a nutrient-rich fluid 10^4 to10^5 times more viscous than water. The yeast metabolism generates intense flow in the underlying fluid substrate several times larger than the unperturbed colony expansion speed. These flows dramatically impact colony morphology and genetic demixing, triggering in some circumstances a fingering instability that allows these organism to spread across an entire Petri dish in roughly 24 hours. We argue that yeast colonies create fluid flow by consuming nutrients from the surrounding fluid, decreasing the fluid's density, and ultimately triggering a baroclinic instability when the fluid's pressure and density contours are no longer parallel. Our results suggest that microbial range expansions on viscous fluids will provide rich opportunities to study the interplay between advection and spatial population genetics.

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Abstract: We re-examine a classic question in liquid-crystal physics: What are the elastic modes of a nematic liquid crystal? The analysis uses a recent mathematical construction, which breaks the director gradient tensor into four distinct types of mathematical objects, representing splay, twist, bend, and a fourth deformation mode. With this construction, the Oseen-Frank free energy can be written as the sum of squares of the four modes, and saddle-splay can be regarded as bulk rather than surface elasticity. This interpretation leads to an alternative way to think about several previous results in liquid-crystal physics. It also leads to a generalized concept of flexoelectricity, and to ideal liquid-crystal deformations in non-Euclidean geometry.

Abstract: Multivalent biopolymers phase separate into membrane-less organelles (MLOs) which exhibit liquid-like behavior. Here, we explore formation of prototypical MOs from multivalent proteins on various time and length scales and show that the kinetically arrested metastable multidroplet state is a dynamic outcome of the interplay between two competing processes: a diffusion limited encounter between proteins, and the exhaustion of available valencies within smaller clusters. Clusters with satisfied valencies cannot coalesce readily, resulting in metastable, longliving droplets. In the regime of dense clusters akin to phase-separation, we observe co-existing assemblies, in contrast to the single, large equilibrium-like cluster. A system-spanning network encompassing all multivalent proteins was only observed at high concentrations and large interaction valencies. In the regime favoring large clusters, we observe a slow-down in the dynamics of the condensed phase, potentially resulting in loss of function. Therefore, metastability could be a hallmark of dynamic functional droplets formed by sticker-spacer proteins.

Abstract: Over the past few years, mounting interests have been attracted in topics involving intrinsically disordered proteins (IDP). Particularly in the fields of protein engineering, supramolecular self-assembly, functional hydrogels and biomechanics, sophisticated design and manufacturing are realized through amalgamating the IDPs with bioactive components. As one type of the most important IDPs, elastin presents multiple extraordinary properties, including good biomechanical characteristics, biopolymeric phase separation behavior, biodegradability and low immunogenicity. These promising features allow elastin-like proteins to be developed as a new generation of functional biomaterials in the context of cross-disciplinary studies. However, it is challenging to supercharge elastin variants for macroscopic assembly of advanced materials. This talk will highlight recent technical advances and practical applications employing Supercharged elastin-like Proteins (SUPs). First, I will introduce the interplay between SUPs and surfactants and soft matter ensembles generated through the two-component complexation. Second, an artificial tongue consisting of SUPs and polyelectrolyte elements for whiskey discrimination will be underscored. Lastly, a recent finding on etiology of Alzheimer's disease and elastin would be presented.

Abstract: Gelation of colloidal suspensions plays a crucial role in the formation of numerous solids. Examples range from cement to yogurt, which results respectively from the aggregation of CSH nanoparticles and casein micelles. In both systems, short-range attractive interactions between the particles lead to the formation of a percolated network that is responsible for the solid-like behavior of the material. Generated by a kinetic arrest, these solids are out-of-equilibrium structures, whose properties are sensitive to the route followed during gelation. Indeed, external shear often comes to compete with the attractive interactions that drive the gelation, affecting the gel's microstructure, which encodes the gel's shear history. Such a "memory effect" is, for instance, easily visualized in the various morphologies of crack patterns that form when the gel is left to dry.

Abstract: Self-organization phenomena that lead to pattern formation and synchronization play an important role in biology, chemistry, physics and technological applications. They manifest for example in electrical waves on the heart muscle, fireflies flashing in unison, power-grid blackouts and neurological functions as well as disorders. I will present a versatile experimental setup based on optically coupled catalytic micro-particles, that allows studying synchronization patterns in very large networks of relaxation oscillators under well-controlled laboratory conditions. In particular I will show the experimental verification of the elusive spiral wave chimera state, whose existence was predicted more than 15 years ago. This pattern features a wave rotating around a spatially extended core that consists of phase-randomized oscillators. The spiral wave chimera is likely to play a role in cortical cell ensembles, arrays of SQUIDS and carpets of cilia. Furthermore, these experimental capabilities facilitate the free choice of network topology, coupling function as well as its strength, range and time delay, which can even be chosen as time-dependent. This opens the door to a broad range of future experimental inquiries into pattern formation and synchronization on large networks, which were previously out of reach.

Abstract: Optical techniques can enable non-invasive, in situ measurements of the properties of biologically or industrially relevant colloidal particles. One such property is the fractal dimension of fractal-like aggregates, which can be formed by some proteins when heated. Here, we consider recent experiments that used holographic microscopy, a technique based on optical interference, and an optical scattering model based on an effective-medium theory to determine the fractal dimension of colloidal aggregates. We numerically generate fractal aggregates with a known structure, simulate the images that would be experimentally obtained from those aggregates, and analyze the simulated images using the proposed scattering model. Our results show that holographic microscopy accurately determines the fractal dimension (to within ~10%) when multiple scattering within the aggregates is negligible. They also suggest that holographic microscopy is useful because it probes the extinction cross section of the aggregates.

Abstract: Smart fluids - or a fluid with suspended particles in which an applied field produces a substantial change in properties - are a fascinating class of soft materials that are widely used in applications ranging from automotive suspension to high performance speakers. However, predicting their performance from first principles remains challenging. Our underlying hypothesis is that a deeper understanding can be gained by studying highly controlled model particles and connecting these to emergent behavior of the system. Here, we explore two model systems, (1) the electric-field directed assembly of nanoparticles and (2) the mechanical properties of particle-laden interfaces. In the first section, we introduce a novel method to measure the polarizability of nanoparticles based upon modest trapping fields and fluorescence microscopy. By using this assay, we determine that nanoparticles can exhibit polarizabilities that are >30 times larger than would be expected based upon simple models, corroborating early theoretical work that includes contributions from space charge in the Debye layer. In the second section, we discuss the mechanical properties of liquid marbles, or drops of liquid coated with a layer of hydrophobic particles that render the entire structure non-wetting. By developing a novel method to study the deformation of liquid marbles, we find that while the elastic mechanics of liquid marbles are invariant of the particle coating, the failure properties of marbles depend strongly on the particle identity, suggesting that more weakly interacting particles constitute tougher marbles. These observations are further explored using a series of macroscopic experiments studying the break-up of particle rafts based on a funnel method. While there remain open questions about the behavior of smart fluids, these lessons illustrate that important insights can be gained by combining novel multi-scale characterization strategies and well-characterized particles.

Abstract: In many biological phenomena, cells migrate through confining environments. To study such confined migration, we place migrating cells in two-state micropatterns, in which the cells stochastically migrate back and forth between two square adhesion sites connected by a thin bridge. We adopt a data-driven approach where we learn an equation of motion directly from the experimentally determined short time-scale dynamics, decomposing the migration into deterministic and stochastic contributions. This equation captures the dynamics of the confined cell and accurately predicts the transition rates between the sites. We thereby derive the emergent non-linear dynamics that governs the migration directly from experimental data. In particular, we find that the deterministic dynamics is poised near a bifurcation between a limit cycle and bistable behaviour. As a result, we find that cells are deterministically driven into the thin constriction; a process that is sped up by noise. Our approach yields a conceptual framework that may be extended to describe cell migration in more complex confining environments.

Abstract: Like mixtures of oil and water, artificial lipid membranes undergo liquid-liquid phase separation. Unraveling the physical mechanisms behind the organization of these liquid phases in membranes is a central goal in biophysics, while the ability to reproduce them in synthetic structures holds great potential for applications in self-assembly and drug delivery. Previous studies on vesicles and supported lipid bilayers have unveiled a fundamental interplay between the membrane geometry and position of different lipid domains. However, the detailed mechanisms behind this coupling remain incompletely understood, because of the difficulty of independently controlling the membrane geometry and composition. In this talk, I will show how we overcome this limitation by fabricating multicomponent lipid bilayers supported by colloidal scaffolds of prescribed shape. Thanks to a combination of experiments and theoretical modeling, we demonstrate that the substrate local curvature and the global chemical composition of the bilayer determine both the spatial arrangement and the amount of mixing of the lipid domains.

Abstract: Packing problems occur in numerous applications, such as granular media under confinement, Pickering emulsions, viral structure, etc. When identical particles are packed occurs on a curved geometry, crystalline order is necessarily disrupted by the curvature, necessitating introduction of defects: a paradigmatic example is the “scars” or grain boundaries found in the packing of spherical particles on a spherical shell. Conversely, for very polydispersed or heterogeneous systems, packings are amorphous. We connect these two regimes by investigating packings as a parameter of particle shape, finding that the spherical crystallography and amorphous regimes are linked by growth and percolation of the scar network. Prospects for experimental realizations of such systems will also be presented.

Abstract: A mixture of particles suspended in a fluid is ubiquitous around us, in nature and applications. When a suspension is sheared, it exhibits a complex, rich and varied behavior such as shear thinning, shear thickening, shrinking or dilating, and so on. Despite extensive available data on mixture reactions to shearing, determination of macroscopic properties of a suspension has remained a challenge, as such mixture properties are dependent on particle systems and sizes, shearing magnitude, experimental duration and experimental methods, even when hydro-clustering is avoided, and the suspension is composed of uniform rotationally-neutral monodispersed spherical particles. At the same time, microstructural ordered states of sheared suspensions have been detected and reported for numerous spherical mixtures. In this presentation, relationships between dynamic and effective ordered states and two components of stress tensor will be explored, the first linear viscosity coefficient and the second normal stress. A proper relationship between these two components will also be developed.

We consider solid spherical particles that are interacting both locally and globally, and form a single effective ordered or unordered structure in the mixture when viscosity is the dominant dissipation mechanism. It is demonstrated that this assumption is sufficient to predicting stress components of the mixture response to an applied shear stress under different conditions, for both colloidal and non-colloidal suspensions, up to but not including the jamming limit. We'll show that our analysis is consistent with the light-scattering observations of Ackerson group in the past decades. For non-colloidal mixtures, both viscosity and the 2nd-particle pressure data confirm the first Ackerson transition at particle volume fractions 45-50%. For colloidal suspensions, the observed non-Newtonian effects such as shear thinning at higher volume fractions or at higher shear-rates coincide with emergence of the second Ackerson transition to a higher-order crystalline state by the shear flow.