MRSEC Seminars

The MRSEC holds seminars presenting research at the frontier of Bioinspired Soft Materials. The seminars are targeted towards graduate students and other researchers in the field, although everyone is invited to attend. As the topic is highly interdisciplinary, seminars are designed to be accessible to a wide range of backgrounds.

The seminars take place on Thursdays at 12:10am in Abelson 229 and on Zoom unless otherwise noted.

Organizers: Thomas Videbaek and Wei-Shao Wei (Rogers/Fraden Lab Postdocs)

2025

Publishing in influential journals

April 10, 2025

Dr.  Shriyaa Mittal, Scientific Editor at Cell Press

Ever wondered how influential journals select content for publication and how peer review works? In this talk, I will discuss the editorial process at these journals, which typically rely on professional editors, focusing in particular on the Cell Press portfolio and introducing Newton, our new flagship physics journal. I will also share my views on current trends in scientific publishing, and provide tips on how to maximize the fit of your manuscript for high-impact journals and on how to deliver an appropriate reviewer report if you are invited to review a manuscript.

Mechanobiology in vivo and in 3D

March 27, 2025

Dr. Keng-hui Lin, Academia Sinica Institute of Physics at Taipei, Taiwan

This talk has two parts. First, we examine mechanical waves during wound healing in zebrafish tailfin regeneration. Using live-cell imaging, we observed cell density waves propagating from the amputation site, with wave travel distance proportional to the extent of injury. We developed a mechanical model relating tension-dependent wave speed and amputation-dependent distance, suggesting mechanical signals drive positional sensing in regenerative tissues.


Second, we describe our work with spherical-cap microwells for 3D cell culture. These wells promote spheroid formation, prevent cell loss, and affect cell proliferation and polarity differently from cylindrical wells. Notably, fibroblasts cultured in spherical microwells experience cell-cycle arrest due to negative curvature, demonstrating unique cellular behaviors resulting from specific 3D geometries compared to traditional 2D environments.

Embedding Symmetries in De Novo Protein Design

March 6, 2025

Dr. Hyunjun Yang, University of California San Francisco

In nature, proteins evolve to refine specific protein-protein interactions (PPIs). Symmetrically configured PPIs enable a single monomer or oligomer subunit to self-assemble into highly ordered, closed supramolecular structures. These assemblies often exhibit remarkable symmetrical architectures—such as the polyhedral symmetry observed in viral capsids or the cyclic symmetry of membrane pores—that confer distinct structural and functional advantages.


De novo protein design, which constructs protein structure and sequence from first principles, offers a platform to probe these symmetrical interactions and decode the fundamentals of PPIs in symmetry. Recent advances in diffusion-based machine learning models have paved the way for the deliberate design of proteins with predetermined symmetric architectures. However, challenges remain, particularly in managing the large size of these assemblies, addressing thermodynamic constraints, and achieving orthogonal PPIs.


In this seminar, I will review the history and key successes of protein design with symmetry in mind and present our current approaches to design proteins with the structural and interaction codes that govern symmetric protein assemblies.

Active Hydrodynamic Models of Organelle Morphodynamics and Nuclear Chromatin Organization

February 6, 2025

Dr. Alex Rautu, Flatiron Institute

Living cells are nonequilibrium systems where active forces, hydrodynamic flows, and mechanical constraints govern intracellular organization. Here, we present continuum hydrodynamic models to investigate two key processes: the active remodeling of endomembrane organelles and the large-scale organization of chromatin in the nucleus. In the endomembrane system, vesicle-mediated fission and fusion drive organelle remodeling through nonequilibrium mechano-chemical processes. These not only regulate membrane area and lumenal volume but also generate active membrane stresses. We find that these active stresses and fluxes drive stable organelle drift and lead to the emergence of elongated, ramified morphologies, capturing key features of Golgi architecture. In the nucleus, chromatin is organized into transcriptionally active euchromatin and silenced heterochromatin, each with distinct mechanical properties and dynamics. We find that contractile stresses from chromatin-binding proteins drive the phase separation of heterochromatin into droplets that grow, coalesce, and wet the nuclear boundary. At the same time, transcriptional activity in euchromatin generates nonequilibrium fluctuations that drive coherent chromatin motions, indirectly deforming heterochromatin and shaping overall chromatin organization. Together, these results provide a framework for understanding how physical forces and active processes shape cellular architecture across different scales.

2024

Self-limited self-assembly

December 5, 2024

Dr. Zvonimir Dogic. UC Santa Barbara

We study the self-assembly of 2D fluid-like membranes. The size-dependent edge tension favors spherical vesicles while size-independent bending energy favors flat disk-like shapes. With increased size, the edge energy dominates, thus generating edgeless vesicles. This mechanical instability limits the self-assembly process to generate monodisperse liquid droplets. Next, we study the pathways by which closed vesicles transform into flat disks. Remarkably, the lowest energy pathway involves a topologically distinct cylinder-like intermediate, which can be understood by considering the energy landscape close to the disk-to-vesicle transition. 

Mechanism and evolution of gasdermin pore formation

November 18, 2024

Dr. Alex Johnson, Brandeis Biochemistry

In response to pathogen infection, gasdermin proteins assemble into membrane pores that induce a host cell death process called pyroptosis. Recent studies indicate that gasdermin-mediated cell death are evolutionarily conserved host defense mechanisms from prokaryotes to mammals. In my seminar, I will describe the discovery of bacterial gasdermins and describe how individual ~30 kDa protomers assemble into gigantic megadalton-sized membrane pores. A structure of one such gasdermin pore determined by single-particle cryo-EM illustrates striking similarities and unexpected differences between bacterial and mammalian active-state gasdermins, and also raises the possibility of a divergent evolution of gasdermins and pore-forming toxins. Based on cell-based and in vitro studies, coupled to molecular dynamics simulations, I propose a model for how evolutionarily conserved gasdermin palmitoylation drives efficient pore formation. Finally, I will discuss new directions to understand the activation and pore formation of evolutionarily conserved pore-forming proteins.

Dynamical arrest in active nematic turbulence

November 14, 2024

Dr. Ido Lavi, Flatiron Institute

Active fluids often display spontaneous, turbulent-like flows known as active turbulence. Recently, research has shown that these flows share universal characteristics, independent of the fluid properties or the presence of topological defects. But how do defect-laden and defect-free active turbulence actually compare? Through large-scale simulations, we find that defect-free active nematic turbulence can enter a dynamically arrested state. Specifically, we observe that flow alignment—the tendency of liquid crystals to reorient under shear—amplifies large-scale jets in contractile systems but promotes dynamical arrest in extensile systems. This produces striking labyrinthine patterns, where an emergent topology of nematic domain walls partially suppresses chaotic flows. Our findings motivate experimental studies on defect-free active nematics and further suggest that true topological defects enable stronger turbulence by breaking the grid-lock of nematic domain walls.

Dynamic Patterns in the Cell Cortex - Energy Dissipation and Deep Learning Applications.

October 31, 2024

Dr. Sheng Chen, Yale University Department of Biomedical Engineering

Intracellular patterns are essential indicators of cellular functionality and the fate. Dynamic phenomena such as spatiotemporal oscillatory actin waves, coupled with signaling pathways, drive fundamental processes like cytokinesis. The topologically structured actin network with locally excess myosin motors leads to the material failure of the cell cortex. Crucially, these patterns often precede these key cellular behaviors, making them potential predictive markers for these events. This talk will review recent advancements from two distinct perspectives to unravel the physical principle underlying these intracellular patterns: (1) The thermodynamic principle governs the energy partitioning in the cell-division-associated mechanochemical waves in the cell cortex (Chen et. al., Nature Physics, 2024); (2) Utilizing deep learning to predict the material failure of the reconstituted cell cortex based on its initial topological structure (Chen et. al., submitted).
3D printing cytoskeletal networks: ROS-induced filament severing leads to surge in actin polymerization

October 10, 2024

Dr. Thomas Litschel, Harvard University School Of Engineering And Applied Sciences


 The cytoskeletal protein actin forms a highly spatially organized biopolymer network essential for many cellular processes, controlled by a complex regulatory system. Here we show that in experiments with purified actin in vitro, a surprisingly simple experimental setup is sufficient to precisely control both actin assembly and actin disassembly. To do so, we use photosensitive molecules such as fluorophores, as a tool to locally generate reactive oxygen species (ROS) upon light exposure. We see that ROS sever actin filaments and thus greatly increase the number of polymerizing filament ends. Our technique enables 3D control of both actin assembly and disassembly and even allows for 'multi-color printing'. Our experimental data is accompanied by simulations using a kinetic model of actin polymerization, which reveal further details about the behavior. In cells, ROS are known to regulate the actin cytoskeleton, but the underlying mechanisms are mostly unknown. Our results suggest that ROS might directly affect actin reorganization in living cells.

Membranes of hungry yeast are tiny, living, phase-separating thermostats

August 30, 2024

Dr. Sarah L. Keller, University of Washington Chemistry

A stunning phase transition occurs in the membranes of living yeast (S. cerevisiae). When nutrients are reduced, membranes of the yeast vacuole, an endosomal organelle, undergo liquid-liquid phase separation to produce micron-scale domains. These domains are functionally important, enabling yeast survival during periods of stress. This talk will review recent results showing: (1) This miscibility transition is reversible as would be expected from equilibrium thermodynamics, even though it occurs in a living system. (2) Yeast actively regulate this phase transition to hold the membrane transition ~15˚C above the yeast growth temperature. (3) In cases when domains appear as stripes, there is no current theory that explains all physical observables of the system.

Modeling assembly of colloids with charges and with mobile binders

June 12, 2024

Dr. Glen Hocky, NYU

In this talk, I will present our recent efforts in probing the physical processes underlying self-assembly of colloidal gels and crystals. Nano-meter to micron sized particles in suspension can be a powerful platform for assembly novel functional materials, but the challenge is to design interactions such that desired functionality is achieved. Moreover, for practical purposes this must be done on a large scale. First, I will discuss our work on using particles with many mobile binding sites, where particles can 'choose' their number of neighbors by assembling adhesion patches between particles. Second, I will discuss nucleation and growth of crystals formed from pairs of charged colloidal particles in suspension.

References
1) Ionic Solids from Common Colloids. Theodore Hueckel, Glen M. Hocky, Jeremie Palacci, and Stefano Sacanna. Nature, 580, 487-490 (2020)
2) Crystal clear: enabling 3D real space analysis of ionic colloidal crystallization. Shihao Zang, Adam W. Hauser, Sanjib Paul, Glen M. Hocky, and Stefano Sacanna. Nature Materials, available online (2024)
3) A Coarse-Grained Simulation Model for Colloidal Self-Assembly via Explicit Mobile Binders. Gaurav Mitra, Chuan Chang, Angus McMullen, Daniela Puchall, Jasna Brujic, and Glen M. Hocky. Soft Matter, 19, 4223-4236 (2023)
4) Mesoscale molecular assembly is favored by the active, crowded cytoplasm. Tong Shu, Gaurav Mitra, Jonathan Alberts, Matheus Viana, Emmanuel Levy, Glen M. Hocky, and Liam J. Holt. In press, Phys Rev X Life (2024)

Models and mechanisms in soft/active matter with topological defects

May 30, 2024

Dr. Robin Selinger, Kent State Advanced Materials and Liquid Crystal Institute
Topological defects play a key role in the properties and dynamics of both passive and active soft matter with nematic order. We will discuss several research directions where confinement geometries control defect behavior, e.g. with boundaries of complex shape or with patterned surface anchoring. First we'll discuss the Frank-Read source mechanism, where defect pinning points drive periodic disclination loop generation in a passive nematic under applied twist [1]. Next we'll give a progress report on agent-based simulation studies of confined active nematics. Lastly we will discuss nematics in contact with patterned substrates to create designer disclination textures [2]; and liquid crystal polymer coatings with stimuli-responsive, switchable topography [3]. In each case we compare model predictions to relevant experiments and discuss potential applications. Work supported by NSF-CMMI-1663041.


[1] Long et al, PRX 2024 https://doi.org/10.1103/PhysRevX.14.011044 [doi.org]
[2] Jiang et al, Liquid Crystals 2023  https://doi.org/10.1080/02678292.2023.2208551 [doi.org]
[3] You et al, Materials Horizons 2024 https://doi.org/10.1039/D4MH00131A [doi.org] (Advance paper)
Finding stability amidst chaos: how dynamic chromatin interactions produce stable epigenetic states

April 25, 2024

Dr. Kaushik Ragunathan, Brandeis Biology

Cells can establish gene expression states that are heritable across multiple generations. This process involves the modification of DNA packaging proteins called histones, which serve as a scaffold for the binding and assembly of complexes that silence or activate gene expression. As a polymer, chromatin has unique properties and serves, at least in part, as a cellular device that can store epigenetic memory, which is stable and heritable across many generations. Interestingly, proteins that interact with histones are simultaneously involved in promoting epigenetic memory and controlling nuclear stiffness. This talk will explore the intersections between chromatin, chromatin-binding proteins, and their roles in regulating gene expression and nuclear mechanics.

Predicting and discovering protein dynamics

April 16, 2024

Dr. Hannah Wayment-Steele, Brandeis Biochemistry & Kern Lab

Thefunctions of biomolecules are often based in their ability to convert betweenmultiple conformations. Recent advances in deep learning for predicting anddesigning single structures of proteins mean that the next frontier lies in howwell we can characterize, model, and predict protein dynamics. I will talkabout two projects from my postdoctoral work in this direction. First, I willdiscuss a method that enables AlphaFold2 to sample multiple conformations ofmetamorphic proteins by clustering the input sequence alignment. This workenabled us to design a minimal set of 3 mutations to flip the populations ofthe fold-switching protein KaiB, as well as screen for novel putative alternatestates. Further development of such bioinformatic methods in tandem with experiments will likely have profound impact on predicting protein energy landscapes, essential for illuminating biological function.

Measuring the Mechanical Behavior of Small, Squishy Bio-Things Using Microfluidics

April 4, 2024

Dr. Joanna Dahl, UMass Boston Engineering

Understanding of the mechanical behavior of microscale biological bodies such as cells and vesicles are important for fundamental cell biology research and for disease diagnostics and therapeutics in clinical settings. Microfluidic devices are ideally suited for studying small, soft objects due to their well-defined laminar flows, transparent material for direct observation, and high-throughput capabilities. With accompanying mechanical modeling, we can perform detailed mechanical analysis of biological soft bodies trapped at the stagnation point or passing through the extensional flow region. This presentation focuses on our current projects performing miniaturized creep tests on biomimetic hydrogel microparticles, exploring how the stiffnesses of large extracellular vesicles from cancer cells vary with lipid-altering mutations,and investigating the continuum of cell spheroid biomechanical behavior with spheroid size.

A tug-of-war determines the directionality of collective EF-guided cell motility

March 21, 2024

Dr. Calina Copos, Northeastern University Mathematics

Galvanotaxis is the migration of cells in response to electric fields (EFs). Notably, EFs have been recorded in biological tissues during wound healing and development. Multiple pathways have been implicated in the mechanisms underlying galvanotaxis, including phosphoinositide 3-kinases (PI3Ks). It has been reported that the electric signal orients both the protrusive actin and contractile actomyosin networks toward the cathode. However, inhibiting PI3K partially disorganizes the protrusive lamellipodium so that the cathode orientation of the actomyosin contractile rear “wins”, re-orienting individual cells to the anode. Here, we report on the motility of control and PI3K-inhibited groups of epithelial keratocytes and a surprising contradictory observation regarding their motility direction. Indifferent of size, control groups migrate to the cathode with larger groups migrating slower. Large groups of PI3K-inhibited cells also move to the cathode BUT smaller groups switch orientation and move to the anode instead. To explain these seemingly contradictory observations, we build a computational model and show that these observations are consistent with the hypothesis that cells within a group respond to the electric field differently depending on their geometrical constraints. 

High-precision measurement of short-ranged colloidal interactions

March 14, 2024

Caroline Martin, Harvard University Physics

Understanding the interactions between colloidal particles is essential for controlling self-assembly, as well as predicting the structures and properties of those assemblies. But characterizing colloidal interactions can be a challenging task. Methods to characterize colloidal interactions generally rely on imaging the particles, usually within an optical potential, and inferring the distribution of distances between them to extract the potential. Such methods must account for the external potential, as well as light scattering between the particles and out-of-plane fluctuations. In this talk, I’ll discuss an alternative method to infer particle pair potentials based on holographic microscopy and Bayesian inference. With this method, we can precisely track pairs of freely-diffusing spheres in three dimensions and at high frame rates, allowing us to precisely characterize the short-ranged attractive and repulsive forces the particles experience.

Modeling the response of soft active materials

March 13, 2024

Dr. Aaveg Aggarwal, Northwestern University

The complex behaviors of living systems stem from their ability to sense and respond to their surrounding environment. Synthetic materials equipped with such sensory mechanisms and shape-morphing capabilities can allow us to create devices that are inherently smart. One such class of materials is hydrogels functionalized with active components. For example, spiropyran hydrogels with embedded magnetic nanowires can interact with both light and magnetic fields. In this talk, I will discuss our continuum models that are used to quantitatively study these interactions and allow us to create controllable soft robots capable of walking and swimming. The interplay between the photochemistry and magnetoelasticity of the hydrogel material, and its hydrodynamic interaction with the surrounding fluid imparts phototactic properties to these swimmers. Furthermore, I will also discuss our work on ferrofluid droplets. Using our continuum models, we show that these droplets can move on solid surfaces under the influence of rotating magnetic fields. Our theoretical and computational models help us better understand these active systems and support their design and development process.

Dynamical Instabilities in 3D Cytoskeletal Materials

March 11, 2024

Dr. Abhinav Singh, Max Planck Institute of Molecular Cell Biology and Genetics

Cytoskeletal mixtures composed of microtubules and Kinesin-1 motors exhibit spontaneous chaotic flow inside 3D channels when sufficient active stress is generated by internal molecular mechanisms. Experiments have revealed the existence of both in-plane and out-of-plane instabilities in such three-dimensional active matter under confinement. However, the emergent dynamics of these materials have been deemed intrinsically chaotic. From three-dimensional active matter theory, we characterize the transition to spontaneous flow, showing that boundary conditions play a key role in the emergent behavior of cytoskeletal materials. Using nonlinear numerical simulations, we elucidate the mechanisms underlying both in-plane and out-of-plane instabilities. We identify distinct regimes of flow and predict the existence of both no-flow and steady-flow states, below and above a critical active potential, respectively. These predicted states were confirmed in recent experiments by altering the confining geometry of the cytoskeletal mixture from channels to droplets.

Negative Energetic Elasticity in Gels: Insights from a Lattice Polymer Chain

February 29, 2024

Dr. Nobu C. Shirai, Center for Information Technologies and Networks at Mie University, Japan

The recent observation of negative energetic elasticity in polymer gels challenges the traditional notion that the elastic moduli of rubberlike materials primarily arise from entropic elasticity. To understand the microscopic origin of this phenomenon, we examined the n-step interacting self-avoiding walk (ISAW) on a cubic lattice [Phys. Rev. Lett. 130, 148101 (2023)]. This model represents a single polymer chain—a subchain in a polymer gel network. Our theoretical investigations, based on exact enumerations up to n=20, reveal the emergence of negative energetic elasticity. The underpinning of this behavior is the attractive interaction between polymer and solvent. This model reproduces the temperature-dependent behavior of negative energetic elasticity observed in polymer gel experiments, suggesting that single-chain analysis can elucidate the properties intrinsic to polymer gel's negative energetic elasticity. Through these insights, our work offers a comprehensive understanding of polymer gel mechanics.

Protein Design Insights from Large Datasets

January 29, 2024

Dr. Joanna Slusky, University of Kansas Molecular Biosciences
Protein design relies on a deep understanding of the mimicked protein category. By constructing a large dataset of outer membrane proteins, we discovered features of outer membrane protein biogenesis and evolution. With a second large dataset—of metalloproteins—we revealed key differences between metal binding sites that can and can’t catalyze reactions. We are now using these datasets to design novel outer membrane proteins and enzymes.
Program Self-Assemblies with Genetic Codes

January 25, 2024

Dr. Shunzi Wang, University of Washington

Nature harnesses genetic sequences to encode structural information and emergent lifeprocesses. Such orchestration is achieved through hierarchical self-assemblies driven by weakmolecular interactions. However, emulating such programmability that evolution has perfected inartificial systems is still an ongoing challenge. The recent development of advancedcomputational tools and machine learning models unlocks many exciting possibilities in thisarea, particularly in designing functional biomaterials with architectures and propertiespreviously deemed unattainable.

In this seminar, I will highlight our recent progress in the rational design of programmable matterusing genetic codes. I will start by discussing our discovery of particle analogs to electrons incolloidal crystals engineered with DNA, unraveling fundamentally new design principles.Building on our insights from colloidal crystals, we designed a novel class of geneticallyencodable materials based on 3D de novo protein crystals with potential intracellularapplications. Lastly, by incorporating reinforcement learning algorithms into protein design, wedeveloped a top-down approach to design geometrically constrained protein architectures aspotent vaccines and modular nanopores. We believe that the ability to program assemblies withDNA and proteins across multiple length scales will catalyze transformative advances in humanhealth and sustainable development.
Artificial Biomolecular Condensates at Soft Living Interfaces

January 16, 2024

Dr. Amal Narayanan, Howard Hughes Medical Institute & Princeton University

The living cell is an intricate and synchronized organization with compartmentalization across diverse length scales. While intracellular compartments such as the lysosome and mitochondria are bound by membranes, cells also contain organelles, not confined by membranes, known as “biomolecular condensates”. Recent studies showed that many biomolecular condensates are viscoelastic materials formed from the phase separation of proteins and nucleic acids. The abrupt changes in composition and material properties of these condensates impair their biological function and are often associated with cancer, ribosomopathies, and aging disorders. Therefore, synthetic systems are required to create model biomolecular condensates in living systems. These systems aim to elucidate the biophysical principles of intracellular organization and diseases.

In the first part of my talk, I will discuss our work on using protein oligomerization and sequence interactions in vivo to create multiphasic biomolecular condensates that mimic native condensate assemblies. We show that specific molecular and nanoscopic design principles can be exploited to design optogenetic fusion proteins that exhibit targeted condensation with high spatiotemporal resolution. Later in this talk, I will describe our work on synthetic polymers to form condensates that mimic the function of underwater adhesive proteins secreted by marine organisms such as mussels and sandcastle worms. In summary, the bioinspired design of macromolecules that form model biomolecular condensates represents new frontiers to ask fundamental questions on the behavior of mesoscopic biological assemblies in living cells and to inspire the design of novel functional materials.

 

Economical routes for size-specific assembly of DNA origami tubules

January 11, 2024

Dr. Thomas Videbææk, Brandeis University MRSEC

Self-assembly is one of the most promising strategies for making functional materials at the nanoscale. Typically, synthetic self-assembly has been limited to spatially unbounded periodic lattice structures. In contrast to this, many biological systems have developed the ability to create complex self-limited structures, such as viral capsids and microtubules. Inspired by these biological systems, we make triangular subunits using DNA origami that have specific, valence-limited interactions and designed binding angles that assemble into tubules. Though we design our subunits to create a specific structure, experiments reveal a broad distribution of tubule types, with varying width and helicity. This is the result of a general challenge in self-limited assemblies, that thermal fluctuations of the inter-subunit binding angles often lead to polymorphism in the final assembly outcome.

Here, we introduce a strategy to eliminate polymorphism by increasing the assembly complexity. By increasing the number of components in the assembly, we can keep the target structure unchanged while reducing the density of off-target states, increasing the selectivity of a user-specified target structure to nearly 100%. These results reveal an economical limit for self-limited assemblies that balances selectivity with assembly complexity up to arbitrary assembly size.

Peptides as Building Blocks for Evolvable Porous Materials

January 5, 2024

Dr. Andy Nguyen, University of Illinois, Chicago

A longstanding goal is to create crystalline porous materials that mimic protein complexity, evolvability, and dynamics. Towards this end, peptides have been pursued as building blocks for porous materials, but success has been very limited due to the difficulty of peptide design and structural characterization. To address these challenges, our laboratory has developed a strategy that reliably generates numerous peptide-based porous crystals by leveraging synthetic and non-canonical moieties. These resulting frameworks have multiple variable positions that enable rapid engineering of complex pore environments reminiscent of protein active sites, and they can utilize flexibility, cooperativity, and site-isolation effects to achieve unique reactivity and host-guest chemistry. Notably, nearly peptide frameworks form single crystal suitable for X-ray diffraction, revealing structural-functional relationships in high detail.
The Good, the Bad, and the Weird of β-Sheets

January 3, 2024

Dr. Hyunjun Yang, UC San Francisco 

The Good: Teixobactin is a potent undecadepsipeptide antibiotic against Gram-positive bacteria that binds to lipid II and related peptidoglycan precursors and disrupts the cell membrane. I present the chemistry of teixobactin. The X-ray crystallographic structures of each teixobactin derivatives reveal the formation of antiparallel β-sheets that creates binding sites for anions.

The Bad: In neurodegenerative diseases, proteins fold into cross-β-sheet motif amyloid structures with distinct conformations (strains). There is a need to rapidly identify these amyloid conformations as well as microenvironment changes in situ. I present (1) EMBER — imaging method that rapidly identifies conformational differences in Aβ and tau deposits from Down syndrome, sporadic and familial Alzheimer’s disease human brain slices and (2) TORCH — de novo design of peptides that bind specific conformers of α-Synuclein.

The Weird : Cross-β-sheet motif of amyloids shares structural characteristics to β-solenoids. During my chalk talk, I will present a de novo protein design pipeline to patch amyloid surface onto a soluble protein and their potential usage as the building blocks for supramolecular assemblies.

2022

Elasticity Theory and Topological Defects in Nematic Liquid Crystals

December 15, 2022

Cheng Long,  Kent State University

Liquid crystal is a state of matter where constituents show orientational order, despite lack of translational order. For regular nematic liquid crystal, the ground state of orientational distribution of mesogens is described by a single axis, known as the director. Due to effects such as surface anchoring or chiral nature of added liquid crystal molecules, the uniformity in an orientational order field can be broken. The short-range spatial correlation persisting in the orientational order field, as well as topological defects enabled by the uniaxial symmetry manifested from the local orientational order of a nematic liquid crystal, often gives rise to abundant intriguing and sophisticated pattern formation in nematic liquid crystals. Studying the pattern formation and the topological defects in those orientational order fields is essential for understanding rheological and optical properties of nematic liquid crystals.

In the first part of my talk, utilizing a reformulated Oseen-Frank elasticity theory invented by J. Selinger, I will demonstrate theoretically that geometric frustration exists in cholesteric liquid crystals. To illustrate how geometric frustration is manifested in cholesteric liquid crystals, I will give two examples. The first example is a cholesteric liquid crystal confined in a long cylinder with free boundaries, where the director field experiences a pattern shift as the size of the cylinder increases and the geometric frustration accumulates. The second example is a cholesteric liquid crystal confined between two infinite parallel plates with free boundaries, and due to geometric frustration, buckled cholesteric helical structures form close to the free boundaries, reminiscent of the Helfrich-Hurault instability. In the second part of my talk, based on the Frank-Read mechanism for the multiplication of dislocations in crystalline solids, I will present an analogous Frank-Read mechanism for disclinations in nematic liquid crystals.

Activity suppressed phase separation and nonequilibrium interface dynamics

December 8, 2022

Fernando Caballero, UC Santa Barbara

Active liquid crystals have become a canonical example of active matter due to the many experimental realizations, theoretical studies, and they're promise to be a pathway to programmable and controllable materials. I will describe some recent developments in which the critical temperature of mixtures of active liquid crystals and equilibrium materials can be controlled with activity, i.e. the temperature at which the system transitions from uniform mixed states to phase separated states can be controlled by changing the strength of the active stresses. This happens as the turbulent flows created by the active nematic provide a self-stirring force, capable of stabilising a uniform state below the critical temperature. I will also introduce the dynamics of the interface of such a system in its phase separated state, which gives information about the kind of arrested phase separation the systems display in its coexistence region, as well as how we can expect structures to coarsen over time.
Drop impact of complex fluids: shear jamming with free surfaces

November 30, 2022

Michelle Driscoll ,  University of Chicago

Complex fluids exhibit a variety of exotic flow behaviours under high stresses, such as shear thickening and shear jamming. Rheology is a powerful tool to characterise these flow behaviours over the bulk of the fluid. However, this technique is limited in its ability to probe fluid behaviour in a spatially resolved way. Here, I will show how we can utilize ultrahigh-speed imaging and the free-surface geometry in drop impact as a new tool for studying the flow of dense colloidal suspensions.   In addition to observing Newtonian-like spreading and bulk shear jamming, we observe the transition between these regimes in the form of localized patches of jammed suspension in the spreading drop. This system offers a unique lens with which to study shear-thickening fluids, allowing us to obtain flow information in a spatially-localized manner, so that we can observe coexisting solid and liquid phases. Furthermore, we capture shear jamming as it occurs via a solidification front traveling from the impact point, and show that the speed of this front is set by how far the impact conditions are beyond the shear thickening transition

Biophysics of cell division and microtubule-motor materials

October 27, 2022

Meredith Betterton, UC Boulder

All life on earth depends on cells’ ability to make more cells. In order to divide successfully, cells must solve fascinating physics problems. To ensure that each of the daughter cells inherits a single copy of the genetic material, a machine called the mitotic spindle builds itself, then exerts forces to physically move the chromosomes. We are using theory, simulation, and experiment to address fundamental physics questions related to mitosis. These include how the mitotic spindle self organizes, how the spindle moves chromosomes, and how these same components outside of cells can create nonequilibrium materials that exhibit new physics. Microtubules are a component of the mitotic spindle that have long been known as highways for transport inside cells.

In part one of the talk, I will discuss recent work which unexpectedly found that the microtubule is not a passive road on which motors move, but instead a responsive medium that allows motors to talk to each other over surprisingly long distances. In the second part of the talk, I will discuss aLENS, a new simulation framework for large-scale microtubule-motor systems that we helped develop. An example problem we have studied using aLENS is active condensation of microtubule-motor mixtures under confinement.
What Rubber and Jello Can Teach Us About Earthquakes and Fractures

October 19, 2022

Will Steinhardt, UC Santa Cruz

Many systems in geophysics, including faults, ice sheets, and hill slopes, are predominantly stable, but become unstable catastrophically, with severe societal consequences when they do. However, the behaviors of these systems are difficult to predict because they involve extreme spatial and temporal scales, accumulating stresses over decades or centuries, but nucleating failure processes in fractions of a second, which start at the micron-scale but lead to kilometers of deformation.

In this talk, I will discuss how I utilize techniques from soft matter physics to build scaled-down experiments that explore these complex problems in systems where a wide range of unique properties can be tuned to make otherwise impossible observations. I will present two examples: First, I will discuss how material heterogeneity leads to brittle fracture roughness, and show that the resultant morphology of a crack is, surprisingly, not dependent upon the details of the medium, but is instead controlled entirely by a single parameter: the probability to perturb the fracture front above a critical size to produce a step-like instability. In addition, we can directly observe the detailed three-dimensional dynamics of this process, and show how they are governed by simple topological rules. Second, using a scaled, transparent laboratory fault where slip at the interface can be directly imaged, I will show that fully confined, slow slip events in our system follow earthquake-like and frictional scaling, but display seismological stress drops that are invariant to not only normal stress, but also normal stress heterogeneity and to a large extent frictional properties. However, this invariance disappears as more ruptures are allowed to reach the edge of the system.

Mechanochemical Defects in an Active Nematic: How to build a reaction- diffusion system that senses topology

October 13, 2022

Michael Norton, Rochester Institute of Technology

Extensile active nematics built from reconstituted biopolymers are known for their intrinsically chaotic material flows and complex defect dynamics. In living active nematics, topological defects can take on functional roles that control cell fates. A striking example is the hydra microorganism, wherein defect patterns in the animal’s supracellular actomyosin network locate its limbs, mouth, and foot. Taken together, these observations from biology suggest the existence of a variety of feedback mechanisms between topological information and biochemistry and, more broadly, diverse strategies for sensing geometry and controlling form. Devising synthetic self-organized systems with comparable internal sensing dynamics would provide opportunities for increasing their functionality.

In this presentation, I ask: what is a simple chemical system that can sense the topology of a nematic? I show that a curvature-dependent reaction dipole is sufficient for creating a system that dynamically outputs topological information in the form of a scalar order parameter possessing local extrema coinciding with +/- 1/2 defects. I demonstrate the behavior of this system for stationary defects and in the presence of active hydrodynamic flows. I also show how this topology sensing system can underpin the construction of additional chemical processes that, in turn, shape the spatiotemporal structure of the active stress strength. I close with a discussion of generalizations to the model and possible experimental implementations of the system. 

Hierarchical design synthesis of active biomaterials

September 8, 2022

Michael Heymann, University of Stuttgart Institute for Biomaterials and Biomolecular Systems

By integrating 3D bioprinting with biomolecular self-assembly and reaction diffusion engineering we seek precisely defined biomaterials with the correct hierarchical organization from the atomic scale to the full organ. We advance two photon stereolithography to create and comprehend biomolecular structure-function relationships across scales. This entails novel ultracompact microfluidic approaches to time-resolved structural biology at X-ray free-electron lasers to record ‘molecular movies’ of macromolecular conformational changes at the atomic scale to determine the transient states with millisecond to second time resolution at atomic spatial resolution. Fabrication precision and 3D flows and mixing dynamics are validated using X-ray microtomography.

In extending this technology to synthetic biology, we reconstitute functional biological and biomimetic systems with unprecedented precision and throughput. We structure the molecules of life (protein, lipid, DNA) into complex 3D reaction compartments, to achieve the highest achievable functional conformity to cellular structures in vivo. These include soft micro-robotics to manipulate lipid membrane vesicles, as well as biomechanical micro-actuators based on 3D printed muscle protein. 3D printed extracellular matrix scaffolds with organotypic biomechanics allow us to guide in vitro 3D organoid formation.

Corresponding algorithmic design synthesis is developed to systematically investigate accessible biological design space for robust in situ material differentiation at the respective scales. These will ultimately refine computer aided design tools to specify desired design shapes and print tool-paths and integrated biomolecular programs for robust self-organization.
Pulsating bubbles swim in anisotropic fluids

August 15, 2022

Joonwoo Jeong, Ulsan National Institute of Science and Technology


Employing thermotropic nematic liquid crystals(LCs) as a continuous phase, we demonstrate that a pulsating bubble accompanying a topological defect can swim in the anisotropic fluid, despite the bubble's symmetric shape and motion. The deformed nematic director field around the bubble provides the centrosymmetry breaking, and the surrounding LC's nematodynamic response to the bubble's pulsation breaks the time-reversal symmetry. Proposing a new mechanism that symmetry breaking solely in a fluid can realize symmetric and reciprocal swimmers, this study deepens our understanding of microswimmers in complex fluids.
If time allows, I will introduce other ongoing and non-LC projects in the Experimental Soft Matter Physics (SOPHY) group at UNIST, with bacteria, microfluidics, and X-ray/neutron imaging.

Building a primitive ‘life cycle’ for fatty acid vesicles

August 4, 2022

Anna Wang, University of New South Wales Sydney


The origins of life from simple molecules required several leaps in complexity. One of the critical structures that must have emerged was the protocell, a primordial cell that could propagate itself and its encapsulated genetic material, that could have eventually evolved into life as we know it.
One subfield of origins of life research focuses on how primordial cell membranes could have carried out the functions necessary for life, prior to the advent protein enzymes. This is fundamentally a soft materials problem. To answer this question, we work with a model system consisting of fatty acids owing to their ability to be synthesised abiotically [1,2]. The fatty acid membranes are highly dynamic compared to phospholipid membranes, leading to surprising outcomes such as the selective self-assembly of giant unilamellar vesicles [3]. The membranes also readily encapsulate RNA, have tunable permeability [4], and can store elastic energy that enables coupled growth and division [3], or even ‘endocytose’ near a nutrient pool.
I will end with a discussion of my interest in these vesicles as colloidal objects, and outstanding questions in the field.
[1] JM Gebicki, M Hicks, Chemistry and Physics of Lipids (1976)
[2] DW Deamer, RM Pashley, Origins of Life and Evolution of the Biosphere (1989)
[3] JT Kindt, JW Szostak, A Wang, ACS Nano (2020)
[4] LA Lowe, JT Kindt, C Cranfield, B Cornell, A Macmillan, A Wang, Soft Matter (2022)

Light Responsive Self-Assembled Gel Systems

May 19, 2022

David Amabilino, Autonomous University of Barcelona

A responsive supramolecular system comprising a bis-imidazolium gelator with a porphyrin and azobenzene photoswitch, both of which are anionic, self-assembles in mixtures of water and ethanol to give a gel which is responsive to light, where the porphyrin moves over micrometer scale distances when irradiated. The movement is instigated and characterized using total internal reflection fluorescence microscopy. The movement is shown to be a result of both photothermal effects and the trans-cis-trans switching of the azo molecule. In the absence of this switch, no motion occurs, but the system acts as a useful material for the generation of singlet oxygen. More recent results on the movement of molecules in these supramolecular systems will be included.

Activity Matters in Organoid Systems

April 7, 2022

Andreas Bausch, Technical University of Munich

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 in organoid systems, demonstrating how mechanical feedback between extracellular matrix, proliferation and cell migration drives structure formation process in these multicellular model systems. I will present results on the developmental phase of mammary gland and pancreatic ducal adenocarcinoma organoids.

Imaging, Learning, and Engineering of Soft Matter Systems at the Nanoscale

February 21, 2022

Vida Jamali, University of California Berkeley

The motion and dynamics of nanoparticles and macromolecules in bulk and at interfaces is of fundamental importance in physics, chemistry, and biology. Liquid phase transmission electron microscopy (LPTEM) is an emerging technique which enables nanoscale visualization of the motion and dynamics of single nanoparticles in liquid environment with an unprecedented spatial and temporal resolution. However, in order to develop LPTEM as a tool for in situ single nanoparticle and macromolecule tracking, we first need to understand how the electron beam of a transmission electron microscope affects the particle motion in the liquid environment and near surfaces.

In this talk, I will present my recent work on studying the anomalous diffusive motion of a model system of gold nanorods dispersed in water and moving near the silicon nitride membrane of a commercial liquid cell in a broad range of electron beam dose rates. By leveraging the power of convolutional deep neural networks inspired by canonical statistical tests, I show that there is a crossover in diffusive behavior of nanoparticles in LPTEM from fractional Brownian motion at low dose rates, resembling diffusion in a viscoelastic medium, to continuous time random walk at high dose rates, resembling diffusion on an energy landscape with trapping sites. I will then discuss how this work forms the foundation to study equilibrium and nonequilibrium dynamic processes for a broad range of nanoparticles, interfaces, and fluids in chemical and biological systems.

Greasing Proteins Wheels: Harnessing Post-translational Lipidation for Bioinspired Materials Science and Engineering

February 17, 2022

Davoud Mozhdehi, Syracuse University

Advances in recombinant DNA technology have expanded our ability to design and produce new protein-based materials with superior control over the biomacromolecule length, sequence, and structure for biomedical applications. Despite these positive attributes, protein-based materials still lack the chemical diversity of their synthetic analogues due to the limited repertoire of canonical amino acids. This limitation significantly restricts the available chemical design space (and thus the function) of protein-based biomaterials. In our quest to overcome this evolutionary constraint, we are inspired by a solution offered by Nature: leveraging specific chemical transformations to modify proteins with non-proteinogenic building blocks, a process called post-translational modification (PTM), which expands the diversity of the proteome by more than two orders of magnitude. 

Our focus is to reprogram unique PTMs to synthesize de novo designed hybrid biopolymers with programmable self-assembly. Our efforts are motivated to answer this fundamental question: What advanced properties can be encoded in protein-based materials by expanding the chemical design space from canonical amino acids to canonical and engineered PTMs? Answering this fundamental question paves the way for utilizing these hybrid biopolymers for new biomedical applications.

In this talk, I will focus on lipidation as a representative class of PTMs. Nearly one in five human proteins are post-translationally lipidated, and while the role of lipidation in regulating different facets of cell biology (e.g., signaling or membrane localization) has been well established, many mechanistic questions remain unanswered. These include the effects of lipidation on the energetics, conformations, and function of lipidated proteins. The progress is further slowed because the existing methods to synthesize LPs are challenging, laborious, and low-yield. 

To address these issues, we have genetically engineered prokaryotes to incorporate a diverse set of lipids into proteins, enabling the rapid generation of comprehensive libraries of model LPs with broad physicochemical diversity. With this library at hand, we used a diverse array of biophysical and soft-matter characterization techniques to correlate the LPs’ molecular syntax to emergent functional/material properties such as nano-assembly and viscoelasticity. This work provides insights into the LP’s design principles—a thermodynamically grounded understanding of the contribution of LP’s molecular syntax to their structure, assembly, and function. These principles contribute to a better understanding of the role of LPs in diverse biological mechanisms and will foster the development of next-generation recombinant biomaterials and therapeutics.

Salt-laden hydrogels as electrical and thermal energy transduction media

February 15, 2022

Tom Schroeder, Harvard University

Being alive involves existing out of thermodynamic equilibrium. Living organisms are full of gradients – in pressure, concentration, electrical potential, and so on. These gradients serve as driving forces that power useful transport processes and chemistry in a manner that is directed by highly specialized biological macromolecules and assemblies such as proteins and lipid membranes. Thanks to developments in the field of polymer science, we are now able to engineer synthetic macromolecules and assemblies with unprecedented precision and ease. Looking often to biology as a showcase of what is possible, I aim to leverage this polymer toolkit to develop useful new energy transduction processes. In this talk, I will discuss two projects in which aqueous electrolyte solutions held out of equilibrium were used to store energy that was subsequently released as heat or electricity. In each case, polymer-based hydrogels functioned simultaneously as physical reservoirs for the solutions and as kinetic barriers that modulated transport and energy release using nanoscale interactions between the polymer and the electrolyte.
In the first project, my colleagues and I took inspiration from electric eels, which contain meter-long organs responsible for generating their trademark discharges, to develop power sources composed entirely of soft, aqueous materials. Eels’ organs are essentially stacks of membranes that separate reservoirs containing solutions with different electrolyte compositions; in the “firing” state, the selectivity of each membrane produces a small electrical potential from the gradient it sustains, and the sum of these potentials can reach over 800 volts at open circuit. We were able to create a similar system that used hydrogels to behave as both electrolyte reservoirs and selective membranes; arrangements of this type can generate over 100 volts and power small devices. In the second project, I devised a means of patterning the fast, exothermic crystallization of metastable supersaturated salt solutions by encapsulating them in hydrogels with unpolymerized pathways. Upon nucleation with a seed, crystal growth through these pathways was significantly faster than in the polymerized bulk. The rapid release of latent heat in these areas produced spatially resolved heat maps which could be used to selectively activate downstream processes.

The Interplay of Geometry and Kinetics in Chemical Transformations of Nanocrystals

February 3, 2022

Layne Frechette, National Institutes of Health

Post-synthetic modification is a promising avenue for chemists to tailor the properties of nanocrystals and to guide their assembly into functional materials. Yet, tuning such properties as nanocrystal shape and composition is often difficult because procedures for doing so take place far from equilibrium. In this talk, I will discuss the progress we have made in understanding two such processes using theory and computer simulation: (i) chemical etching, which produces concentration-dependent transformations of nanocrystal shape, and (ii) cation exchange, in which spontaneous swapping of ions of different identities effects compositional change. In both cases, geometry plays a key role in determining the outcomes of these nonequilibrium transformations.
Engineering the Ideal Membrane for in vitro Tissue Barrier and Cellular Co-Culture Models

January 24, 2022

Thomas Gaborski, Rochester Institute of Technology

Physiologically relevant in vitro tissue barrier and co-culture models are instrumental in investigating the mechanisms of drug delivery, leukocyte transmigration, cancer metastasis, and cell-cell communication during disease progression. Porous substrates are an indispensable part of many barrier model and tissue-on-chip platforms, but are largely treated as just another off-the-shelf component. Our laboratory has developed a variety of ultrathin and optically transparent nano- and micro-porous membranes to better to understand the ideal properties for these systems. We investigated engineering pore size and pore spacing to tune and control cell-substrate and cell-cell interactions. We found that reducing pore-pore spacing generally weakens cell-substrate interactions, as evidenced by fewer focal adhesions and reduced nuclear YAP in endothelial and mesenchymal stem cells, similarly to very soft substrates. On the other hand, endothelial cells on these same membranes have enhanced cell-cell interactions with more robust ZO-1 labeling, confirming a trade-off between cell-cell and cell-substrate interactions during monolayer formation. We further demonstrated that micron and submicron pore size influence early cell-substrate interaction and behavior in terms of migration and the associated extracellular matrix deposition and fibrillogenesis. These results suggest that membrane parameters can be engineered for specific cell types and tissues to promote improved in vitro barrier properties and potentially mimic softer tissue-like substrates.

From Cryo-EM of Microbial Pili to EM-based Nanotube Design

January 20, 2022

Fengbin Wang, University of Virginia

Abstract: In this seminar, Dr. Wang will first talk about cryo-EM studies of microbial pilis, particularly their roles in pathologies (bacterial T4P), microbial ecology (archaeal T4P), and bioenergetics(cytochrome nanowires). However, the biomaterial and biomedical applications of those fascinating filaments are limited by the fact that none of the microbial pili can self-assemble, and they were put together by massive transmembrane secretion systems.

Inspired by biological helical assemblies, Dr. Wang will present a few collaborative projects about bringing self assembled peptide-based nanotubes into biomaterial and biomedical applications, and then further discuss the crucial role of cryo-EM in the rational designs of nanotubes.