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 11:10am in Abelson 229 and on Zoom unless otherwise noted.
Organizers: Thomas Videbaek and Wei-Shao Wei (Rogers/Fraden Lab Postdocs)
March 28, 2024Dr. Kaushik Ragunathan, Brandeis University
March 21, 2024
Dr. Calina Copos, Northeastern University
March 14, 2024Dr. Caroline Martin, Harvard University
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.
January 29, 2024
January 25, 2024
Dr. Shunzi Wang, University of Washington
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.
January 16, 2024
Dr. Amal Narayanan, Howard Hughes Medical Institute & Princeton University
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.
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.
January 5, 2024
Dr. Andy Nguyen, University of Illinois, ChicagoA 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.
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.
December 16, 2023
Dr. Julien Tailleur, MITEquilibrium statistical mechanics tells us how to control the self-assembly of passive materials by tuning the competition between energy and entropy to achieve desired states of organization. Out of equilibrium, no such principles apply and self-organization principles are scarce. In this talk I will review the progress which has been made over the past ten years to control the organization of self-propelled agents using motility control, either externally or through interactions. I will show that generic principles apply and illustrate the theoretical developments presented in the talk using recent experiments on run-and-tumble bacteria. In particular, I will discuss the fate of non-reciprocal interactions between swimming bacteria and show that non-reciprocity has a subtle fate upon coarse-graining. Finally, I will show some form of universality and how different interactions at the microscopic scale, like chemotaxis and quorum-sensing, may coarse-grain into a unique description at large scales.
November 29, 2023
Dr. Becki Yi Kuang
Synthetic mRNAs, which have the ability to directly produce functional proteins inside living cells, hold the power to revolutionize the biomedical industry. The work by Karikó, Weissman, and other researchers realized the first clinical use of base-modified synthetic mRNA as vaccines against SARS-CoV-2. Nevertheless, current synthetic mRNAs are still challenged by limited translatability and stability, which constrain the development of new mRNA tools.
In this talk, I will discuss our current efforts in enhancing the performance of synthetic mRNAs using base modification and tail sequence optimization. Facilitated by these newly discovered enhancement technologies, we have engineered a model anti-cancer vaccine to stimulate stronger immune response for tumor suppression. We have also developed several mRNA devices that can manipulate cell fate through controlled supramolecular assembly. In addition, I will introduce our on-going work on designing therapeutic mRNA to inhibit cancer progression. Engineering advanced synthetic mRNAs not only unveils new mRNA regulatory mechanisms that deepen our understanding of mRNA biology but also opens new avenues for building new mRNA tools to mitigate healthcare challenges
November 28, 2023
Dr. Ludwig Hoffmann
Cluster formation of microscopic swimmers is key to the formation of biofilms and colonies. However, in the absence of other interactions, high swimmer concentrations are required in order for clustering to occur. I will present our recent results showing that cluster formation can be dramatically enhanced by the microscopic swimmers having an anisotropic geometry. We analyzed a class of model microswimmers with a shape that can be continuously tuned from spherical to bent and straight rods. We find that the clustering dynamics of a bent rod is fundamentally different from the straight and spherical shapes that are usually studied, and that the anisotropy promotes assembly even at vanishingly low particle densities. I will present experimental and theoretical results on the density-dependent clustering dynamics of anisotropic active particles, as well as an analysis of the shape-dependency of clustering.
November 13, 2023
Dr. Jason Green
Whether living or synthetic, systems that assemble multiscale structures or generate power in finite time must also pay the price of energy dissipation and entropy production. For example, the assembly and disassembly of fibrous supramolecular structures in hydrogels dissipates both energy and waste material. These materials are chemically active, with the kinetics of chemical reactions at the molecular scale having a strong influence over how transient and dissipative the assembly of fibers will be at the mesoscopic scale. Recent experiments have demonstrated the ability to control the spatiotemporal behavior of these dissipative materials with light, chemical reagents, or electricity, creating potential for applications ranging from drug delivery to tissue engineering. However, these applications are not yet fully realized because of the strong connection between microscopic kinetics and mesoscopic behavior, which makes it necessary to (i) directly observe the structural and morphological dynamics at each scale and compare with (ii) predictions of the material behavior and its timed execution from molecular properties. In this talk, I will discuss a reaction-diffusion model of these materials that agrees with the first direct observations using liquid-phase electron microscopy. I will also discuss our thermodynamic speed limits, which are a possible design principle for any system that balances the tradeoff between dissipation and speed. These bounds have theoretical connections to regression analysis and, therefore, existing machine learning techniques, making them a possible theoretical device to optimize energy efficiency and timed structure formation in dissipative materials.
October 26, 2023
October 19, 2023
Dr. Tony Gao
Active matter, a class of materials composed of self-driven microparticles, exhibit probably the wealthiest yet most exotic non-equilibrium behaviors (e.g., density fluctuation, ordering transition). They provide new means of energy conversion from local fuel to mechanical work, and have inspired novel designs of active materials. In this talk, I will review our recent computation and modeling works of various active systems to uncover their underlying multiscale origins of unstable dynamics.
First, I will present direct simulations of dense active particle assemblies such as bacterial swarming and motor-driven biopolymer assemblies. Our new particle simulator fully resolves short- (e.g., collisions) and long (e.g., hydrodynamic)-range interactions between complex-shaped particles. The discrete-particle data from large-scale simulations are then be used to construct bottom-up, coarse-grained PDE models for macro-scale modeling. Under this multiscale modeling framework, I will illustrate how the local particle-particle interactions lead to large-scale collective dynamics via a concatenation of hydrodynamic instabilities. Moreover, I will show examples of building “living” soft machines by leveraging activity, coherent structures, and geometric confinements. In addition, I will briefly introduce our ongoing projects regarding robotics, rheology, and biomedicine.
Dr. Tong (Tony) Gao is an Associate Professor at the Department of Mechanical Engineering and Department of Computational Mathematics, Science, and Engineering at Michigan State University, where he directs the Complex Fluids Group. He obtained his Ph.D. degree in Mechanical Engineering at the University of Pennsylvania in 2012. Then he worked as a research scientist in the Applied Mathematics Lab at the Courant Institute of Mathematical Sciences of New York University. Dr. Gao works in the interdisciplinary areas of soft condensed matter, fluid mechanics, and materials via mathematical modeling and high-performance computing. His expertise lies in constructing advanced computational mechanics models for fluid-solid systems with high complexities and nonlinearity, and developing scalable simulation tools to promote data-driven, physics-informed studies. Dr. Gao received the NSF CAREER award in 2020. The current focused research topics include soft condensed matter, soft robotics, and patient-specific medical models.
October 18, 2023
Because the life-cycle of a virus involves neither self-replication nor metabolism, it is often assumed that free energy minimization is the natural theoretical frame work to describe viral assembly. Indeed, free energy minimization can account quantitatively for the self-assembly of viral capsids that do not contain specifically selected viral genome molecules. The talk will discuss why recent experimental studies of the assembly of both small viruses, such as the MS2 virus, and large viruses, such as the HIV-1 virus, rule out the notion that free energy minimization can describe the assembly process. Simple non-equilibrium statistical physics descriptions will be presented for the genome selection and assembly processes of MS2-like viruses and of retroviruses like HIV-1.
September 28, 2023
Dr. Layne Frechette (Hagan Lab) & Jeremy Laprade (Duclos Lab)
When immersed in an active fluid, soft materials can self-organize and fluctuate in novel and striking ways. Yet understanding these active composites is challenging because their behavior emerges from processes acting across multiple time and length scales. We propose a framework for modeling such systems, in which the active fluid is treated as a noise that is correlated in both space and time. Inspired by experiments on passive actin networks immersed in an active microtubule fluid, we use theory and computer simulations to study elastic networks driven by such a spatiotemporally correlated noise. Our results demonstrate that the interplay of elasticity and active driving forces can give rise to new kinds of collective motions, whose behaviors depend on the relationship between the characteristic time and length scales of the activity and those of the elastic network.
September 21, 2023
Alison Sweeney | Yale University
Living photosynthetic systems can be near-perfectly efficient at solar energy conversion at small length- and time-scales. However, they are very inefficient (~3%) at the scale of crops or ecosystems. Is it physically possible to realize the near-perfect efficiencies of photosynthesis at a small scale over large land areas? Answering this question is crucial for reducing economic reliance on fossil fuels. We created a simple model of a "solar transformer" that was inspired by the geometry of symbiotic giant clams that host single-celled algae in their tissues. We found a straightforward, general mechanism to achieve a photosynthetic light-use efficiency of 67% of the solar radiance in an average tropical day. Remarkably, living clams may exceed this efficiency, and we describe additional mechanisms that may allow this.
August 31, 2023
Pragya Arora and Nick Berg | Brandeis University
DNA origami is a versatile technique used to make defined nanostructures out of single-stranded DNA scaffolds. One facet in the expansive scope of origami research is the design of constructs that associate with lipid bilayers and self-assemble. By targeting origami to lipid substrates, we can achieve functions including the complete and cooperative encapsulation of enveloped viruses, which outperforms the efficiency of independent antibody binding events. However, gauging the effectiveness of a lipid-targeted origami construct requires methods to visualize single-molecule kinetics and assembly dynamics. Here we present a TIRF microscopy system for evaluating the behaviors of DNA origami triangles on a supported lipid bilayer. Within our system, origami with special modifications to enable bilayer association and fluorescent signal can be consistently tracked at single molecule resolution in real time. We have demonstrated both robust diffusion of origami as well as stable, reversible self-assembly on the bilayer surface, and can determine origami-bilayer and origami-origami binding kinetics. These data will allow us to predict the effectiveness of monomer designs in various real-world applications. Our TIRFm platform is reliable and adaptable, and may be expanded to accommodate other lipid-associated DNA origami designs.
June 16, 2023
Rumayel Pallock , University of Nebraska - Lincoln
Active fluids in biological and artificial systems are governed by fully nonequilibrium dynamics, and their emergent spatiotemporal structures span multiple scales. The dominant flow patterns of such systems can be understood in a systematic manner in terms of Exact Coherent Structures (ECS) and the dynamical pathways connecting them. An ECS is a (stable or unstable) equilibrium, time-periodic, relative time-periodic, quasi-periodic or traveling wave solution of the governing equations, while their invariant manifolds form the connecting pathways between different ECS. The ECS framework enables a fully nonlinear but highly reduced-order description in terms of a directed graph. We provide a unified study of stable and unstable coherent states of 2D active nematic channel flow using the framework of ECS. We compute more than 150 unstable ECS that co-exist at a single set of parameters in the weakly `active turbulent' regime. Using the reduced representation, we compute instantaneous perturbations that switch the system between disparate spatiotemporal states occupying distant regions of the infinite-dimensional phase space. By comparing with simulations in the active turbulence regime, we also provide numerical evidence of a chaotic trajectory shadowing various ECSs.
June 16, 2023
Angel Naranjo, University of Nebraska - Lincoln
Equivariance and symmetries have been known to play a major role in deciding the phenomenology of nonlinear continuum systems such a classical fluid dynamical systems that govern atmospheric (e.g., Rayleigh-Bernard convection) and industrial (Poiseuille flow) processes. We will highlight the role of equivariance and symmetries in active nematic channel flow. Specifically, we will discuss the numerical observation of certain exotic flow states, e.g., spontaneous reversals of unidirectional flow along a periodic channel, and outline a strategy for understanding their origin using the language of group theory and nonlinear dynamics.
June 15, 2023
Dr. Linna An, University of Washington Institute for Protein Design
Recent advances in machine learning achieved breakthroughs in protein structural prediction, and opened up a lot of opportunities in the protein engineering field. Designing proteins-small molecules (SM) interfaces has been one of the most challenging problems in the field due to its large sampling space and requirement of high accuracy. Nature often binds to SM through creating great shape complementary (SC) at the protein-SM interface, which sets the foundation for optimal binding energies. Enlightened by Nature, we designed a variety of de novo proteins with different folds and center pockets suiting different SMs, which we referred to as pseudocycles. To identify the individual pseudocycles which provide the best potential to bind to particular SMs, we performed a stepwise in silico structure to sequence sampling. We first performed large-scale docking and design of SMs bound to all 9838 pseudocycle folds. A round of yeast surface display of the designs were used to identify the potential binding scaffolds. We further performed another round of in silico fine sampling of local structure and sequence design between the found scaffolds and the SM to improve binding interfaces. As expected, for each SM, only particular folds with great SC were proven to be optimal, and we were able to identify more than one binders from the same selected pseudocycle fold for our ligands, cholic acid (CHD) and methotrexate (MTX). Using only computational design, we obtained CHD binders from 5 nM to uM. We were able to obtain 1 co-crystal structure for CHD to verify our designs. Through this stepwise sampling of protein-ligand interface SC, we repeated how nature generates small molecule binding interfaces in silico, and developed a general method for de novo SM binder design.
Ref: Linna An*, Derrick R Hicks*, Dmitri Zorine*, et. al. Hallucination of closed repeat proteins containing central pockets, doi: https://doi.org/10.1101/2022.09.01.506251
May 30, 2023
Dr. Luca Giomi, Instituut-Lorentz at Universiteit Leiden
Biological processes such as embryogenesis, wound healing and cancer progression, crucially rely on the ability of epithelial cells to coordinate their mechanical activity over length scales order of magnitudes larger than the typical cellular size. While regulated by various signalling pathways, it has recently become evident that this behavior can additionally hinge on a minimal toolkit of physical mechanisms, of which liquid crystal order is the most prominent example.
In this talk, I will review our ongoing theoretical and experimental efforts toward deciphering liquid crystal order in epithelial tissues and its role in facilitating cells' collective migration.
In particular, I will show that certain kind of epithelial tissues feature a unique combination of nematic (i.e. 2-fold) and hexatic (i.e. 6-fold) order, coexisting at different length scales. Specifically, hexatic order is prominent at the cellular scale, while nematic order characterizes the structure of the monolayer at larger length scales. This hierarchal structure is expected to complement the complex network of regulatory pathways that tissues have at their disposal to coordinate the activity of individual cells to achieve multicellular organization.
May 18, 2023
Niels Bradshaw, Brandeis University
Rod shaped bacterial cells divide using a treadmilling polymer network composed of FtsA (related to actin) and FtsZ (related to tubulin) that is positioned at the midcell by the positioning regulators MinCD. Once a ring of FtsAZ polymers form and condense they recruit cell-wall synthesis enzymes that build septal cell-wall, which drives the separation of daughter cells. To make endospores, B. subtilis cells reposition this dynamic polymer network near the cell poles to generate daughter cells of unequal size, which generates de novo asymmetry in cells size and leads to differentiation of the spore. The transmembrane protein SpoIIE is responsible for repositioning cell-division for endospore formation, but its mechanism of action was unknown. Using a combination of live-cell single-molecule and epifluorescence microscopy, genetics, and protein structure prediction with AlphaFold2, we discovered that SpoIIE repositions FtsZ rings by counteracting MinCD and shortening otherwise abnormally long FtsZ filaments to promote polar FtsAZ ring positioning. Then SpoIIE promotes constriction of polar divisome rings, a function that requires the transmembrane domain of SpoIIE. Finally, we present evidence that SpoIIE promotes septum constriction by directly recruiting the cell wall synthesis complex to polar sites.
May 16, 2023
Mike van der Naald, University of Chicago
Suspensions of solid particles in a liquid can show a range of remarkable material behaviors from shear thickening (ST), where the viscosity can increase orders of magnitude under applied shear stress, to even shear jamming (SJ), where the system solidifies under stress. In the last decade, studies demonstrated that suspending particles interacting frictionally undergird both ST and SJ. In this talk, I will show how we used this new understanding of the mechanism behind ST and SJ to tell two different stories: the first experimental and the second computational. First, I will demonstrate how we used solvation forces to tune the propensity for suspensions to form frictional contacts, thereby controlling the suspensions' ability to ST and SJ. Second, I will show how we imported ideas from rigidity theory to ascertain if the networks of frictional contacts are minimally rigid and how these minimally rigid force networks shape the flow.
May 4, 2023
Nicholas Cuccia, Harvard University
In today's modern world, thin-walled structures, ranging from colloidal membranes to rocket ships, have become an essential component of various applications. Shells, in particular, offer a higher strength-to-weight ratio compared to other geometries, making them ideal for designing lightweight mechanical structures. However, the widespread implementation of shells is hindered by their complex buckling behavior, which can result in catastrophic structural failures, turning once elegantly symmetrical objects into unusable debris. Defects --- imperfections or irregularities in the shape or material properties of a structure --- strongly influence a shell's response to external loads. Although the importance of defects is well-recognized, an understanding of the nuanced relationship between the failure properties of real shells and their defects remains elusive.
We have developed an experimental system that allows for direct, non-destructive, characterization of a commercial cylindrical shell's geometric defect structure (w0) as well as its radial deformations (w) under axial loads (Fa). Traditionally, shell's are thought to be highly sensitive to defects, with their deformations and buckling properties being strongly dependent on the precise details of every small dent and bump along the shell's surface. Contrary to this understanding, our results reveal that defects allow for an uniformly applied axial load at the boundary to be converted into an entirely localized deformation along the shell's surface which is weakly dependent on the underlying defect structure. We observe these localized deformations to exhibit universal features akin to those observed in phase transitions.
By contextualizing these findings within the framework of bifurcation analysis, we gain new fundamental insights into the role of localization and imperfections in the failure of thin shells. Collectively, these results pave the way for novel non-destructive techniques for predicting the buckling properties of shells, potentially enabling engineers to implement new solutions that were once considered impossible.
April 27, 2023
Michael Moshe, Hebrew University of Jerusalem
Holes in elastic metamaterials, defects in 2D curved crystals, localized plastic deformations in amorphous matter and T1 transitions in epithelial tissue, are typical realizations of stress-relaxation mechanisms in different solid-like structures, interpreted as mechanical screening. Correspondingly, understanding the emergent hole patterns, defects structure, and mechanical response in these systems remains a formidable task.
While screening theories are well established in other fields of physics, e.g. electrostatics, a unifying theory of mechanical screening applicable to crystalline, amorphous, and living-cellular matter, is still lacking. In this talk I will present a general mechanical screening theory that generalizes classical theories of solids, and introduces new moduli that are missing from the classical theories. Contrary to its electrostatic analog, the screening theory in solids is richer even in the linear case, with multiple screening regimes, predicting qualitatively new mechanical responses. Specifically, we predict a regime of screening that is mechanically similar to the celebrated Hexatic phase, in disordered matter. The theory is tested in different physical systems, among which are disordered granular solids and models of epithelial tissue. Experiments and numeric simulations in granular, glass, and tissue models uncover a mechanical response that strictly deviate from classical elasticity, and is in full agreement with the theory. Finally I will discuss the relevance of the theory to other systems such as wrinkled sheets, disordered metamaterials, and most importantly to 3D solids and the potential for a new Hexatic-like state in three-dimensional matter.
April 20, 2023
Dorothee Kern, Brandeis University
Why can we not design efficient enzymes or highly selective drugs to date? While one can solve
high resolution structures of ground states experimentally, and even now predict them with Alphafold; for biological function proteins need to traverse the entire energy landscape from the lowest energy state over the transition states into higher energy states. Therefore, I will first 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 (1). Second, a novel general method to determine high resolution structures of high-energy states that are often the biologically reactive species will be described (2). 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 (3).
To gain insight into one of the most fundamental evolutionary events, the development of circadian
rhythms, we find and characterize the most ancient, primitive biological clock (4). Finally, visions (and
success) for putting protein dynamics at the heart of drug design are discussed.
Fig.1: Transition state ensembles (TSE) for adenylate kinase rate limiting conformational change
combining high pressure NMR dynamics with MD simulations (left) and TSE for designed enzyme
(middle) and after directed evolution (right) for Kemp eliminase using x-ray crystallography ensemble
refinement of transition state analogue (TSA) bound enzymes.
1. J. B. Stiller et. al., Probing the Transition State in Enzyme Catalysis by High-Pressure NMR Dynamics
2019, Nature Catalysis (2019) 2, 726–734
2. J. B. Stiller et. al., Structure Determination of High-Energy States in a Dynamic Protein Ensemble
Nature 2022, 603, 528–535
3. R. Otten et. al., How directed evolution reshapes energy landscapes in enzymes to boost catalysis
Science 2020, 2020 Dec 18;370(6523):1442-1446.
4. W. Pitsawong et al., From primordial clocks to circadian oscillators Nature 2023, 616(7955):183-189.
April 19, 2023
Minu Varghese, University of Michigan
Growing tissues are nature's feedback controlled active materials. The emergent mechanics of these systems have been studied experimentally by tracking the evolution of closed curves, or clone boundaries, in plant and animal tissues. However, the underlying feedback laws that give rise to these emergent behaviors are not well understood. We adopt a continuum field theoretic description for a growing tissue and investigate the implications of different kinds of growth laws on the predicted shapes of clone boundaries. We find that the noise and anisotropy associated with biological growth processes rule out some kinds of growth laws while allowing others.
April 18, 2023
 P. Chandrakar et al., "Confinement Controls the Bend Instability of 3D Active Liquid Crystals,'' Phys. Rev. Lett., vol. 125, p. 257801, Dec. 2020.
 A. Singh et al., "A C++ expression system for PDEs in biological hydrodynamics," Eur. Phys. J. E 44, 117 (2021).
 A. Singh et al., "3D Spontaneous Flow Transition in Active Polar Fluids," arXiv:2302.04259 (2023)
February 16, 2023
Thomas Gerling, Technische Universität München
In this presentation, I will showcase the vision of three recently founded companies in Munich that leverage DNA origami technology to create novel solutions in the fields of DNA sequencing, immunotherapy, and antivirals.In the first part of the talk, I will provide an overview of current DNA sequencing technologies and their flow cell design, highlighting the challenges of functionalizing surfaces. Tilibit Nanosystems offers a rather simple solution to enhance throughput of flow cells, thus reducing cost of DNA sequencing. In the second part, I will briefly talk about the two other companies. Plectonic Biotech, which is developing a DNA origami switch to attach various antibodies for anti-cancer immunotherapy. And lastly, I will touch on Capsitec's efforts to develop broad-spectrum antivirals by using DNA origami shells.
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.
December 8, 2022
Fernando Caballero, UC Santa Barbara
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
October 27, 2022Meredith 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.
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.
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.
September 8, 2022Michael 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.
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.
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 . The membranes also readily encapsulate RNA, have tunable permeability , and can store elastic energy that enables coupled growth and division , 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.
 JM Gebicki, M Hicks, Chemistry and Physics of Lipids (1976)
 DW Deamer, RM Pashley, Origins of Life and Evolution of the Biosphere (1989)
 JT Kindt, JW Szostak, A Wang, ACS Nano (2020)
 LA Lowe, JT Kindt, C Cranfield, B Cornell, A Macmillan, A Wang, Soft Matter (2022)
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.
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.
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.
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.
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.
February 3, 2022
Layne Frechette, National Institutes of Health
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.
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.