On a fast timescale, neurons mostly interact by short, stereotypical electrical impulses or spikes. Why? A common answer is that spikes are useful for long-distance communication, to avoid alterations while traveling along axons. But as it turns out, spikes are seen in many places outside neurons: in the heart, in muscles, in plants and even in protists. From these examples, it appears that action potentials mediate some form of coordinated action, a timed event. From this perspective, spikes should not be seen simply as noisy implementations of underlying continuous signals (a sort of analog-to-digital conversion), but rather as events or actions. I will give a number of examples of functional spike-based interactions in living systems.

The emergent dynamics exhibited by collections of living organisms often shows signatures of symmetries that are broken at the single-organism level. At the same time, organism development itself encompasses a well-coordinated sequence of symmetry breaking events that successively transform a single, nearly isotropic cell into an animal with well-defined body axis and various anatomical asymmetries. Combining these key aspects of collective phenomena and embryonic development, we describe here the spontaneous formation of hydrodynamically stabilized active crystals made of hundreds of starfish embryos that gather during early development near fluid surfaces. We describe a minimal hydrodynamic theory that is fully parameterized by experimental measurements of microscopic interactions among embryos. Using this theory, we can quantitatively describe the stability, formation and rotation of crystals and rationalize the emergence of mechanical properties that carry signatures of an odd elastic material. Our work thereby quantitatively connects developmental symmetry breaking events on the single-embryo level with remarkable macroscopic material properties of a novel living chiral crystal system.

The cytoskeleton has the remarkable ability to self-organize into active materials which underlie diverse cellular processes ranging from motility to cell division. Actomyosin is a canonical example of an active material, which generates cellularscale contractility in part through the forces exerted by myosin motors on actin filaments. While the molecular players underlying actomyosin contractility have been well characterized, how cellular-scale deformation in disordered actomyosin networks emerges from filament-scale interactions is not well understood. In this talk, I’ll present work done in collaboration with Sebastian Fürthauer and Nikta Fakhri addressing this question in vivo using the meiotic surface contraction wave seen in oocytes of the bat star Patiria miniata as a model system. By perturbing actin polymerization, we find that the cellular deformation rate is a nonmonotonic function of cortical actin density peaked near the wild type density. To understand this, we develop an active fluid model coarse-grained from filament-scale interactions and find quantitative agreement with the measured data. The model makes further predictions, including the surprising prediction that deformation rate decreases with increasing motor concentration. We test these predictions through protein overexpression and find quantitative agreement. Taken together, this work is an important step for bridging the molecular and cellular length scales for cytoskeletal networks in vivo.

Changes in the geometry and topology of self-assembled membranes underlie diverse processes across cellular biology and engineering. Similar to lipid bilayers, monolayer colloidal membranes studied by the Sharma (IISc Bangalore) and Dogic (UCSB) Labs have in-plane fluid-like dynamics and out-of-plane bending elasticity, but their open edges and micron length scale provide a tractable system to study the equilibrium energetics and dynamic pathways of membrane assembly and reconfiguration. First, we discuss how doping colloidal membranes with short miscible rods transforms disk-shaped membranes into saddle-shaped minimal surfaces with complex edge structures. Theoretical modeling demonstrates that their formation is driven by increasing positive Gaussian modulus, which in turn is controlled by the fraction of short rods. Further coalescence of saddle-shaped surfaces leads to exotic topologically distinct structures, including shapes similar to catenoids, tri-noids, four-noids, and higher order structures. We then mathematically explore the mechanics of these catenoid-like structures subject to an external axial force and elucidate their intimate connection to two problems whose solutions date back to Euler: the shape of an area-minimizing soap film and the buckling of a slender rod under compression. A perturbation theory argument directly relates the tensions of membranes to the stability properties of minimal surfaces. We also investigate the effects of including a Gaussian curvature modulus, which, for small enough membranes, causes the axial force to diverge as the ring separation approaches its maximal value.

An equation of state is something you hear about in introductory thermodynamics, for example, the Ideal gas equation. The ideal gas equation relates the pressure, volume, and the number of particles of the gas, to its temperature, uniquely defining its state. This description is possible in physics when the system under investigation is in equilibrium or near equilibrium. In biology, a tissue is modeled as a fluid composed of cells. These cells are constantly interacting with each other through mechanical and chemical signaling, driving them far from equilibrium. Can an equation of state exist for such a messy interacting system? In this talk, I show that the presence of strong cell-cell interaction in tissues gives rise to a novel non-equilibrium, size-dependent surface tension, something unheard of for classical fluids. This surface tension, in turn, modifies the packing of cells inside the tissue generating a size-dependent density and pressure. Finally, we show that a combination of these non-equilibrium pressure and densities can yield an equation of state for biological tissues arbitrarily far from equilibrium. In the end, I discuss how this new paradigm of size-dependent biological properties gives rise to novel modes of cellular motion in tissues

The fusion of cell aggregates widely exists during biological processes such as development, tissue regeneration, and tumor invasion. Cellular spheroids (spherical cell aggregates) are commonly used to study this phenomenon. In previous studies, with approximated assumptions and measurements, researchers found that the fusion of two spheroids with some cell type is similar to the coalescence of two liquid droplets. However, with more accurate measurements focusing on the overall shape evolution in this process, we find that even in the previously-regarded liquid-like regime, the fusion process of spheroids can be very different from regular liquid coalescence. We conduct numerical simulations using both standard particulate models and vertex models with both Molecular Dynamics and Brownian Dynamics. The simulation results show that the difference between spheroids and regular liquid droplets is caused by the microscopic overdamped dynamics of each cell rather than the topological cell-cell interactions in the vertex model. Our research reveals the necessity of a new continuum theory for “liquid” with microscopically overdamped components, such as cellular and colloidal systems. Detailed analysis of our simulation results of different system sizes provides the basis for developing the new theory.

Macromolecular protein complexes perform essential biological functions across life forms. A fundamental, though yet unsolved question in biology is how the function of such complexes is regulated by intracellular or extracellular signals. For instance, we have little understanding of how forces affect multi-protein machines whose function is often mechanical in nature. We address this question by studying the bacterial flagellar motor, a large complex that powers swimming motility in many bacteria. This rotary motor autonomously adapts to changes in mechanical load by adding or removing force-generating ‘stator’ units that power rotation. In the bacterium Escherichia coli, up to 11 units drive the motor at high load while all the units are released at low load. We manipulate motor load using electrorotation, a technique in which a rapidly rotating electric field applies an external torque on the motor. This allows us to change motor load at will and measure the resulting stator dynamics at single-unit resolution. We found that the force generated by the stator units controls their unbinding, forming a feedback loop that leads to autoregulation of the assembly. We complemented our experiments with theoretical models that provide insight into the underlying molecular interactions. Torque-dependent remodeling takes place within seconds, making it a highly responsive control mechanism, one that is mediated by the mechano-chemical tuning of protein interactions.

The aim of this half day virtual meeting is to consider what is currently achievable with existing techniques and to explore where advancements can be made in the short and medium term. Leading scientists in the field will highlight the questions currently being addressed using hard X-ray imaging techniques, volume electron microscopy and their combination with other imaging modalities, with a forward look to areas of opportunity becoming accessible as a result of the recent and upcoming synchrotron upgrades. We expect an exciting day filled with science focused talks and lively discussions on how the field will develop over the next few years.

Chromosomes are extremely long, active polymers that are spatially organized across multiple scales to promote cellular functions, such as gene transcription and genetic inheritance. During each cell cycle, chromosomes are dramatically compacted as cells divide and dynamically reorganized into less compact, spatiotemporally patterned structures after cell division. These activities are facilitated by DNA/chromatin-binding protein motors called SMC complexes. Each of these motors can perform a unique activity known as “loop extrusion,” in which the motor binds the DNA/chromatin polymer, reels in the polymer fiber, and extrudes it as a loop. Using simulations and theory, I show how loop-extruding motors can collectively compact and spatially organize chromosomes in different scenarios. First, I show that loop-extruding complexes can generate sufficient compaction for cell division, provided that loop-extrusion satisfies stringent physical requirements. Second, while loop-extrusion alone does not uniquely spatially pattern the genome, interactions between SMC complexes and protein “boundary elements” can generate patterns that emerge in the genome after cell division. Intriguingly, these “boundary elements” are not necessarily stationary, which can generate a variety of patterns in the neighborhood of transcriptionally active genes. These predictions, along with supporting experiments, show how SMC complexes and other molecular machinery, such as RNA polymerase, can spatially organize the genome. More generally, this work demonstrates both the versatility of the loop extrusion mechanism for chromosome functional organization and how seemingly subtle microscopic effects can emerge in the spatiotemporal structure of nonequilibrium polymers.

Filaments (slender, microscopic elastic bodies) are prevalent in biological and industrial settings. In the biological case, the filaments are often active, in that they are driven internally by motor proteins, with the prime examples being cilia and flagella. For cilia in particular, which can appear in dense arrays, their resulting motions are coupled through the surrounding fluid, as well as through surfaces to which they are attached. In this talk, I present numerical simulations exploring the coordinated motion of active filaments and how it depends on the driving force, density of filaments, as well as the attached surface. In particular, we find that when the surface is spherical, its topology introduces local defects in coordinated motion which can then feedback and alter the global state. This is particularly true when the surface is not held fixed and is free to move in the surrounding fluid. These simulations take advantage of a computational framework we developed for fully 3D filament motion that combines unit quaternions, implicit geometric time integration, quasi-Newton methods, and fast, matrix-free methods for hydrodynamic interactions and it will also be presented.