Student Poster Abstracts

Somiealo Azote epse Hassikpezi Email Syracuse University	Predicting the biomechanical drivers of cell delamination in stratified epithelia using a dynamic 3D Vertex Stratified epithelial tissues, such as skin and gut, comprise major organs in humans and perform multiple functions, including serving as a barrier to mechanical insults and pathogens. They are constantly self-renewing: balancing stem cell proliferation in the basal layer with a tightly controlled differentiation program in which cells move upward while undergoing stepwise transcriptional and cell shape changes to form the distinct suprabasal layers. Understanding how mechanosensitive mechanisms at the scale of molecules couple to the collective mechanical behavior of the self-renewing tissue, allowing cells to move upward across the sharp basal- suprabasal boundary to regulate stratified tissue homeostasis, is thus essential. Although some delamination events are coupled to cell division, we first focus on the simpler case where delamination occurs in the absence of cell division, and develop a biomechanical model to investigate several experimentally driven hypotheses for what drives delamination those cases: i) changes in the adhesion of basal cells to extra cellular matrix in the basement membrane, ii) local fluidization of surrounding tissue due to fluctuations or nearby cell divisions, or iii) cell autonomous changes to cell-cell adhesion and cortical tension. We investigate these hypotheses using computational simulations of a novel dynamic 3D Vertex model of stratified epithelia, recently developed in our group. Experimental data from the developing mammalian epithelium in the Niessen and Wickström labs have identified specific changes to the transcriptome of cells committed to delamination. Many of these changes are associated with cell-cell and cell-substrate adhesion pathways. We incorporate them in the computational models as changes to the model parameters describing heterotypic and homotypic cell-cell interfacial tensions and adhesion to a fiber network substrate. We make quantitative predictions for cell shapes, delamination probabilities, and delamination speeds that we compare directly to experiments, in both control and perturbed systems, in order to determine how different mechanisms are driving delamination. Future work will focus on understanding delamination coupled with cell division.
Agnish Kumar Behera Email University of Chicago	Correspondence between Hebbian Unlearning and Non-equilibrium steady states In a previous work (arXiv:2203.03024), we demonstrate that an associative memory system with active dynamics can improve the system’s information storage and retrieval properties. Here, we propose an equivalence between the Hebbian Unlearning algorithm (also known as “dreaming”) and modifying dynamics by driving the spins with exponentially correlated noise. We demonstrate that this is similar to how neurons integrate information and fire. Our method shows how neurons can store new memories through different dynamics, without altering existing connections.
Saraswat Bhattacharyya Email University of Oxford	Phase Separation driven by Active Flows We study the hydrodynamics of an active nematic fluid mixed with another passive or active fluid. We model this by extending the continuum theories of active nemato-hydrodynamics to a two-fluid mixture with separate velocity fields for each fluid component, coupled through a viscous drag. We observe phase separation, and argue that this results from an interplay between active anchoring and active flows driven by concentration gradients. The results are an example of liquid-liquid phase separation out of equilibrium, and may be relevant to cell sorting.
Lara Braverman Email Harvard University	Dynamical Billiards on the surface of tilted cones Crystals often grow on 3d surfaces embedded in 2d. The curvature of the surface effects the formation of crystalline structures and the interaction between defects causing grain boundaries as well as other patterns of disclinations and dislocations. Hence, statistical mechanical properties such as ergodicity of dynamical systems on 2d surfaces with varying boundaries are of interest. Here, we extend the well studied dynamical billiard problem with boundaries in 2d onto curved surfaces by placing it on flat surfaces with a conical singularity. It is well-known that a dynamical billiard system on a table with a circular boundary is integrable. In this poster, we demonstrate that either adding curvature or breaking azimuthal symmetry, by setting an elliptical boundary, alone is not sufficient to achieve chaos. However, the addition of both of these changes is. Surprisingly, in this novel chaotic system, unlike in previously studied systems, we observe that chaos can be achieved even with smooth convex boundary conditions. In addition, we also observe more common properties of chaos such as intermittent chaos in our system.
Aravind Chandrasekaran Email University of California, San Diego	Kinetic trapping determines actin filament organization, thereby controlling the shape of liquid droplets Biomolecular condensates are known to act as concentrators of essential proteins resulting in amplification of cellular signaling. The role of condensates in controlling the dynamics of cytoskeleton is not fully understood. Recent evidence suggests Vasodilator stimulated phosphoprotein (VASP) forms liquid droplets and can nucleate, polymerize, and bundle actin filaments to enclose shell and ring-shaped actin networks (Graham et al., Nature Physics, 19, 574–585 (2023)). To understand the mechanism of formation, we used CytoSim, an agent-based actin network simulator and studied the role of VASP-actin interactions under hard wall boundary conditions (https://doi.org/10.1101/2023.05.26.542517). Our simulations reveal that (un)binding kinetics determine the probability of shell vs. ring formation consistent with kinetically trapped structures. We also show that reduction of Actin-VASP residence time would favor shell formation and also establish it with experimental studies. Additionally, we show that rings are only formed under a small subset of conditions studied that provide effective bundling and form at a higher probability under slower filament elongation rates. To highlight the role of nucleation, we study the competition between Arp2/3 and VASP to show that Arp2/3 inhibits ring formation through nucleation of actin filaments (https://doi.org/10.1101/2023.06.23.546267). Experimental evidence also suggests that spherical liquid droplets deform to form ellipsoidal droplets explained by the balance between actin bending and droplet surface energies. We study the reorganization within our simulated droplets containing actin rings and show that filament length plays a critical role in determining whether the ring would eventually become a linear bundle (sphere-to-rod) or if they would remain kinetically trapped in a ring-like structure (sphere-to-ellipsoid). Our findings are relevant to the understanding of the kinetic and mechanical principles that guide the organization of filamentous actin networks within phase-separated liquid droplets.
Yuzhu Chen Email University of California, San Diego	Interplay Between Mechanosensitive Adhesions and Membrane Tension Regulates Cell Motility The initiation of directional cell motion requires symmetry breaking that can happen with or without external stimuli. During cell crawling, forces generated by the cytoskeleton and their transmission through mechanosensitive adhesions to the extracellular substrate play a crucial role. In a recently proposed one-dimensional model [P. Sens, Proc. Natl. Acad. Sci. USA 117, 24670 (2020)], a mechanical feedback loop between force-sensitive adhesions and cell tension was shown to be sufficient to explain spontaneous symmetry breaking and multiple motility patterns through stick-slip dynamics, without the need to account for signaling networks or active polar gels. We extend this model to two dimensions to study the interplay between cell shape and mechanics during crawling. Through a local force balance along a deformable boundary, we show that the membrane tension coupled with shape change can regulate the spatiotemporal evolution of the stochastic binding of mechanosensitive adhesions. Linear stability analysis identifies the unstable parameter regimes where spontaneous symmetry breaking can take place. Using simulations to solve the fully coupled nonlinear system of equations, we show that, starting from a randomly perturbed circular shape, this instability can lead to keratocyte-like shapes. Simulations predict that different adhesion kinetics and membrane tension can result in different cell motility modes including gliding, zigzag, rotating, and sometimes chaotic movements. Thus, using a minimal model of cell motility, we identify that the interplay between adhesions and tension can select emergent motility modes.
Tanumoy Dhar Email University of California, San Diego	Active fluctuations, transport and directed assembly of passive colloids by run-and-tumble microswimmers The mechanism of colloidal aggregation is of significant interest in a diverse range of physical phenomena. In the classical scenario of Brownian motion, colloidal self-assembly is driven by diffusion of microscopic constituents, for example, a suspension of particles in a fluid. Upon aggregation, these particles collide and stick together, forming clusters. Clusters formed solely due to the Brownian motion of their component often demonstrate a slow development of the microstructure. Recent works have shown that active particles show promise in driving colloidal self-assembly. However, the mechanisms governing the out-of-equilibrium assembly of passive colloids suspended in a bacterial suspension are not yet fully understood. This clustering phenomenon is a direct consequence of the interplay of enhanced colloidal diffusion [1] and active depletion forces [2] induced by the run-and-tumble microswimmers. As a first step, we analyze the dispersion of a passive colloid immersed in a bath of non-interacting and non-Brownian run-and-tumble microswimmers in two dimensions using stochastic simulations and a statistical theory, both based on a minimal model of swimmer-colloid collisions characterized solely by frictionless steric interactions [1]. Long-time stochastic simulations reveal the existence of an effective attractive force between a pair of fixed colloids [2], akin to the depletion force arising in the suspensions of polymer coils. Finally, we adapt our computational model accounting for large-scale particle simulations, where we study the kinetics of aggregation and fragmentation for colloids subject to short-ranged tunable adhesive interactions and explore the phase behavior of the colloid-swimmer mixture. We also account for the curvature in the circular trajectories of the swimming bacteria, for example, E. Coli, which emerges from their hydrodynamic interaction with solid surfaces. The long-time statistics of these colloidal aggregates exhibit slow persistent rotations, which we explain using a semi-analytical model. References: [1]: Dhar, T. and Saintillan, D., 2024. Active transport of a passive colloid in a bath of run-and-tumble particles. Scientific Reports, 14(1), p.11844. [2]: Dhar, T. and Saintillan, D., 2024. Active depletion forces and agglomeration of adhesive colloids by run-and-tumble microswimmers. (In preparation).
Daniel Evans Email University of California, Berkeley	Mechanical Insights into Multicomponent Coexistence: A General Theory for Nonequilibrium Systems Nonequilibrium multicomponent systems, such as non-reciprocally interacting systems and mixtures of active and passive particles, routinely experience phase coexistence. In equilibrium, thermodynamics provides a framework to determine the phase diagram of these systems solely from measurable, bulk equations of state. Out of equilibrium, however, it is unclear if phase diagrams can always be constructed solely from bulk equations of state. Here, we leverage balance laws to develop a theory of multicomponent coexistence that is purely mechanical, finding a framework akin to thermodynamics under certain conditions. We find general bulk criteria for coexistence and demonstrate when an effective equilibrium form is admitted. Lastly, we numerically validate our theory on common models of nonequilibrium multicomponent field dynamics.
Joel Hochstetter Email University of Cambridge	Mechanochemical feedback model for squamous tissue maintanence Throughout adult life epithelial tissues are constantly turned over, demanding a delicate between cell loss and replenishment through division and differentiation of stem cells. Using a 2D Voronoi model with division and death, we propose a potential feedback mechanisms for squamous tissue maintenance based competition for biochemical fate determinants, which can robustly converge to a homeostatic steady state from different initial conditions and enables control of the fractions of different cell-types. We study the key phenomenology in terms of clonal dynamics, patterning and phase behaviour at homeostasis. In non-homeostatic conditions, such as mutant clone competition and recovery to homeostasis, we identify distinct predictions between this model and local mechanical feedback models. Through applying our model to in vivo long-term time-lapse experiments, we find a stem/progenitor hierarchy with specific temporal correlations of cell fate are needed to explain the fate behaviour of mouse skin homeostasis. As of yet our results cannot distinguish our chemical feedback mechanism from a local mechanical feedback. However, integrating spatiotemporal data from mutant and regeneration experiments may pave the way forward.
Chanin Kumpeerakij Email University of Colorado at Boulder	Quasi-Stable states in swarmalators: navigating the landscape of active glassy systems In this work, my supervisors and I studied the collective dynamics of a swarmalator with delayed interaction in a dimensions system. Swarmalators are particles that swarm in spatial space while also possessing a cyclic internal degree of freedom – oscillators that swarm. This idea was originally motivated by a swarm of bacteria where internal chemical cycles behave like oscillators. In the paper [1], the authors found that adding a delay can give rise to a long breathing transient – with the radial oscillatory motion of all particles in complete synchrony, resulting in a contraction and expansion of the whole cluster. Following the transient, the system enters a quasi-stationary pseudo-crystalline state, reminding in many ways of glassy behavior. In this work, we study this state in detail. We found that during this stage, the system continues to relax via a gradual increase in global hexatic order parameter. This increase takes place through a series of local velocity hotspots. Each hotspot alleviated local frustration, leaving behind an increased local hexatic order parameter. As the system ages, the quantity of coordination number defects in the bulk decreases, suggesting that bulk crystallization tends to occur naturally in our 2D system. Furthermore, we also found that the more extended breathing state, according to time delay, gives rise to bulk crystallization when compared between short and long delays. Our detailed investigation of the quasi-stable state has demonstrated an exciting mechanism of aging of an active matter system. [1] Blum, N., Li, A., O’Keeffe, K., & Kogan, O. (2024). Swarmalators with delayed interactions. Physical Review. E, 109(1–1), 014205. doi:10.1103/PhysRevE.109.014205.
Samantha Lish Email Oxford University/Max Planck Institute for Dynamics and Self-Organization	The Non-Equilibrium Statistical Embryo How do collectively organized multi-cellular life forms emerge from the exchange of individual mechanical and morphogenetic cues? Deciphering multiscale population dynamics poses a fundamental challenge to understanding the mechanism whereby embryonic growth is coordinated on larger scales. Coupling high-resolution optical imaging with non-equilibrium statistical analysis provides phenomenological insight into the role of mechanics and shape on macroscopic ordering during embryogenesis. Establishment and maintenance of asymmetric pre-patterning in the C. elegans embryo is an ideal subject for statistical exploration of self-assembly, however a physical theory of development from germ layer specification through morphogenesis is lacking. Analyzing stochastic trajectories according to cell fate distinctions and generation dependent control was found to be a robust statistical strategy for defining transition points at which collective space-time morphological patterns emerge. Significantly, oscillations in anomalous diffusion during gastrulation suggest that periods of relaxation accompany waves of collective motion and an increase in super diffusive behavior from differentiated cells suggests that non-equilibrium activity shifts from being driven by proliferation to directed motion. Our data-driven theoretical approach identifies self-organization principles governing proliferation in confinement and yields a new perspective about the embryo as active matter.
Xiao Ma Email University of Cambridge	Hyperuniformity at the Absorbing State Transition Hyperuniform systems, whereby the static structure factor (or density correlator) obeys S(q)~q^h with h > 0, emerges at criticality in systems having multiple absorbing states, such as periodically sheared suspensions. These lie in the conserved directed percolation (C-DP) universality class, for which analytic results for h are lacking. Here, using Doi-Peliti field theory for interacting particle systems and performing perturbative renormalization group about a Gaussian model, we find h=0+ and h=2ε/9+O(ε^2) in dimension d > 4 and d = 4−ε respectively. We show how hyperuniformity emerges from anticorrelation of strongly fluctuating active and passive densities, and highlight the significance of an ‘irrelevant’ conserved noise.
Jessica Metzger Email MIT	Exceptions to the ratchet theorem and their marginal stability Breaking time-reversal and left-right symmetries in stochastic dynamics generically leads to steady-state density currents (ratchet currents) – a principle known as the “Ratchet Theorem.” In active matter, a typical example is active particles in an asymmetric potential. An interesting exception is non-interacting self-propelled particles in an asymmetric activity landscape, which does not lead to steady currents. Surprisingly, the ratchet current is restored by including interactions between the particles. We show this exception to the ratchet theorem (among others) possesses a hidden time-reversal symmetry, which is marginally stable. We explain the interaction-induced ratchet current through a mean-field picture.
Amir Shee Email Northwestern University	Emerging States in Dense Systems of Chiral Active Particles Across scales, from molecules to tissues, dense biological systems can exhibit collective dynamics driven by activity and elastic interactions, including flocking transitions and long-range spatiotemporal order. In this work, we consider densely packed systems of active Brownian particles with intrinsic individual chirality from a theoretical perspective, showing that these can lead to the emergence of a variety of states, including collective rotating mesoscopic order. Using dual analytical approaches—one based on normal modes and the other on continuum elasticity—this study provides a comprehensive understanding of the states that can be observed in the systems, matching very well our numerical simulations. Our findings suggest that the collective rotating states that we identify may generically appear in natural and artificial dense chiral active systems.
Christian Vanhille Campos Email Institute of Science and Technology Austria	Self-organisation of mortal filaments and its role in bacterial division ring formation Filaments in the cell commonly treadmill. Driven by energy consumption, they grow on one end while shrinking on the other, causing filaments to appear motile even though individual proteins remain static. This process is characteristic of cytoskeletal filaments and leads to collective filament self-organization. Here we show that treadmilling drives filament nematic ordering by dissolving misaligned filaments. Taking the bacterial FtsZ protein involved in cell division as an example, we show that this mechanism aligns FtsZ filaments in vitro and drives the formation of the division ring in living Bacillus subtilis cells. We find that ordering via local dissolution also allows the system to quickly respond to chemical and geometrical biases in the cell, enabling us to quantitatively explain the ring formation dynamics in vivo. Beyond FtsZ and other cytoskeletal filaments, our study identifies a mechanism for self-organisation via constant birth and death of energy-consuming filaments.
Kent Wilson Email University of Washington	Sterol-lipids enable large-scale, liquid-liquid phase separation in membranes of only two components A wide diversity of membranes, from those with hundreds of lipids (as in vacuoles of living yeast cells) to as few as three (as in artificial vesicles) phase separate into micron-scale liquid domains. This limit of three components is perplexing from a theoretical standpoint: only two components should be necessary. It is equally perplexing from an experimental standpoint: only two lipid types are required to form large-scale liquid domains in lipid monolayers. This incongruity inspired us to search for single, joined “sterol-lipid” molecules that replace both a sterol and a phospholipid in membranes undergoing liquid-liquid phase separation. By using sterol-lipids with long, saturated chains, we sought to mimic known preferential interactions between cholesterol and lipids with high melting temperatures. We find that membranes with only two components (one of which is a sterol-lipid) do indeed phase-separate into micron-scale liquid domains. This result mitigates experimental challenges in determining tie-lines and in maintaining constant chemical potentials of lipids as lipid ratios are changed. For one of the binary membranes, we construct a miscibility phase diagram to show how the membrane’s phase separation depends on temperature and the ratio of the lipids.
Aaron Winn Email University of Pennsylvania	Oscillatory Flow Networks with Valves Zero Reynolds number Newtonian fluids exhibit perfect time-reversal symmetry even when flowing through highly asymmetric static geometries. However, flexible structures coupled to fluid forces can act as valves and promote preferential flow in one direction. Inspired by the lymphatic system, we study the flow response of a system driven by peristalsis through channels containing valves. Taken together, peristalsis with valves can act like a pump to drive fluid against adverse pressure gradients. When the valve asymmetry is small, the flow response can be decoupled into a purely peristalsis term and a term describing the rectification of oscillations by valves. When the valve asymmetry is large, flow is prevented in the reverse direction, so even at large amplitudes, retrograde peristalsis cannot drive flow against the valve direction. In this regime, the flow is independent of the direction of peristaltic waves and grows proportional to the amplitude of peristalsis. This observation has been confirmed experimentally and quantified using a non-reciprocity metric analogous to that in mechanical meta-materials. This effect becomes even more apparent in networks with branches and loops where it is argued that valves should be placed in such a way as to prevent percolating clusters containing no valves.
Qian-Ze Zhu Email Harvard University	Proofreading mechanism for colloidal self-assembly Designing components that can robustly self-assemble into structures with biological complexity is a grand challenge for material science. Proofreading and error correction is required to improve assembly yield beyond equilibrium limits, using energy to avoid kinetic traps in the energy landscape. Here we introduce an explicit two staged proofreading scheme for patchy particle colloidal assemblies that substantially improves assembly yield and robustness. The first stage implements local rules whereby particles increase their binding strengths when they detect a local environment corresponding to a desired target. The second stage corrects remaining errors, adding a reverse pathway inspired by kinetic proofreading. The scheme shows significant yield improvements, eliminating kinetic traps, giving a much broader temperature range with high yield. Additionally, the scheme is robust against quenched disorder in the components. Our findings illuminate a pathway for advancing programmable design of synthetic living materials, potentially fostering the synthesis of novel biological materials and functional behaviors.