Calendar of MRSEC Events

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

Eduard Xatruch (@disfrutarbcn) Disfrutar and Compartir Barcelona

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

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

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

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

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

Leila Deravi, Northeastern University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

Abstract: TBD abstract

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

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

Fiorenzo Omenetto, Tufts University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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

Dragana Rogulja, Harvard University Medical School
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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Josef Käs, Leipzig University
1:00pm – 2:00pm (EST) | Remote

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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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"

Zhenwei Ma, Harvard University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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2nd Fluids & Health Conference
Mt. Holyoke College (50 College Street, South Hadley, MA)

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

John Zimmermann, Harvard University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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Sponsored by the Harvard MRSEC
11:00 AM to 1:00 PM | Pierce Hall 209 (29 Oxford St, Cambridge)

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

Please register before attending

Hyoungsoo Kim, Korea Advanced Institute of Science and Technology, Korea
10 am to 2 pm | Pierce Hall 209 (29 Oxford St, Cambridge)

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

Max Bi, Department of Physics, Northeastern University
Dr. Dave Weitz's Lab, 9 Oxford St - LISE 424

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

Max Bi, Department of Physics, Northeastern University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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Benny Davidovitch, UMass Amherst
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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Gwennou Coupier, Grenoble Alpes University, Laboratoire Interdisciplinaire de Physique
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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Dorothee Kern, Brandeis University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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Richard Henshaw, Tufts University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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.

Guillaume Duclos, Department of Physics, Brandeis University
1:00pm – 2:30pm (EST) | Remote

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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Amélie Chardac, Department of Physics, Brandeis University
6 - 7:30pm | Pierce Hall 301, 29 Oxford Street

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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Guillermina Ramirez-San Juan, Brandeis University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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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Ben Simons, Cambridge University
1:00pm – 2:30pm (EST) | Remote

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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John Berezney, Department of Physics, Brandeis University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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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Colm Kelleher, Department of Molecular and Cellular Biology, Harvard University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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.

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Georg K. Gerber, MD, PhD, MPH; Associate Professor of Pathology, Harvard Medical School
4 - 5pm EST | Remote meeting

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

Benjamin Freedman, Wyss Institute, Harvard University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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.

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Katherine Copenhagen, Princeton University
1:00pm – 2:30pm (EST) | Remote

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.

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Qiaoling Huang, Department of Physics, Xiamen University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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

Dr. Travis Gibson
12 - 1pm, 24 Oxford Street, Room 375, Cambridge, MA

Rafael Gomez-Bombareli, MIT
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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.

Amin Doostmohammadi, Niels Bohr Institute, University of Copenhagen
1:00pm – 2:30pm (EST) | Remote

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

Pepijn Moerman, Department of Chemical and Biomolecular Engineering, Johns Hopkins University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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.

Dr. Ana Paula Guedes Frazzon
12 - 1pm, 24 Oxford Street, Room 375, Cambridge, MA

Alexandre Bisson, Department of Biology, Brandeis University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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.

Margaret Gardel, University of Chicago
1:00pm – 2:30pm (EST) | Remote

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

Daniel Pearce, Department of Mathematics, MIT
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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.

Qiang Cui, Department of Chemistry, Boston University
6 - 7:30pm | Pierce Hall, room 301, 29 Oxford Street

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.

Petros Koumoutsakos, Harvard University
1:00pm – 2:30pm (EST) | Remote

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