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Cell motility is fundamental to many biological processes, and cells exhibit a variety of migration patterns. Many motile cell types follow a universal law that connects their speed and persistency, a property that can originate from the intracellular transport of polarity cues due to the global actin retrograde flow. This mechanism was termed the ``Universal Coupling between cell Speed and Persistency"(UCSP). Here we implemented a simplified version of the UCSP mechanism in a coarse-grained ``minimal-cell" model, which is composed of a three-dimensional vesicle that contains curved active proteins. This model spontaneously forms a lamellipodia-like motile cell shape, which is however sensitive and can depolarize into a non-motile form due to random fluctuations or when interacting with external obstacles. The UCSP implementation introduces long-range inhibition, which stabilizes the motile phenotype. This allows our model to describe the robust polarity observed in cells and explain a large variety of cellular dynamics, such as the relation between cell speed and aspect ratio, cell-barrier scattering, and cellular oscillations in different types of geometric confinements., Comment: 7 Figures, 10 SI Figures, 18 SI Movies, and 1 SI table

Migratory and tissue resident cells exhibit highly branched morphologies to perform their function and to adapt to the microenvironment. Immune cells, for example, display transient branched shapes while exploring the surrounding tissues. In another example, to properly irrigate the tissues, blood vessels bifurcate thereby forcing the branching of cells moving on top or within the vessels. In both cases microenvironmental constraints force migrating cells to extend several highly dynamic protrusions. Here, we present a theoretical model for the shape dynamics and migration of cells that simultaneously span several junctions, which we validated by using micropatterns with an hexagonal array, and a neuronal network image analysis pipeline to monitor the macrophages and endothelial cell shapes and migration. In our model we describe how the actin retrograde flow controls branch extension, retraction and global cell polarization. We relate the noise in this flow to the residency times and trapping of the cell at the junctions of the network. In addition, we found that macrophages and endothelial cells display very different migration regimes on the network, with macrophages moving faster and having larger changes in cell length in comparison to endothelial cells. These results expose how cellular shapes and migration are intricately coupled inside complex geometries.

Active particle systems of interacting self-propelled particles offer a versatile framework for modeling complex systems. When employed to describe aspects of animal behavior, the complexity of animal movement and decision-making often requires the use of unique types of effective interactions between the particles -- notably nonreciprocal effective forces that do not obey the usual conservation laws of Newtonian mechanics. Here we review two recent empirically-motivated models, of two very different types of animal behavior, where the behavior is described in terms of active particles which interact through nonreciprocal effective forces. The first model describes the dynamics of animal contests, wherein typically two rivals fight over a localized resource. The uniquely shaped effective potentials between the model's 'contestant particles' manifest the adversarial nature of contest interactions and capture the dynamical essence of contest behavior in space and time. The second model describes the stabilization of cohesive swarms through long-range and adaptive gravity-like attraction. This 'adaptive gravity' model explains the observed mass and velocity profiles of laboratory midge swarms. These examples demonstrate that theoretical models that use the framework of active particles to describe animal behavior can expand the scope of active-particle research, as well as explain complex phenomena in animal behavior., Comment: Contributed chapter to the book "Active Particles, Volume 4"

Animals must constantly make decisions on the move, such as when choosing among multiple options, or "targets", in space. Recent evidence suggests that this results from a recursive feedback between the (vectorial) neural representation of the targets and the resulting motion defined by this consensus, which then changes the egocentric neural representation of the the options, and so on. Here we employ a simple model of this process to both explore how its dynamics account for the experimentally-observed abruptly-branching trajectories exhibited by animals during spatial decision-making, and to provide new insights into spatiotemporal computation. Essential neural dynamics, notably local excitation and long-range inhibition, are captured in our model via spin-system dynamics, with groups of Ising-spins representing neural "activity bumps" corresponding to target directions. Analysis, employing a novel "mean-field trajectory" approach, reveals the nature of the spontaneous symmetry breaking - bifurcations in the model that result in literal bifurcations in trajectory space and how it results in new geometric principles for spatiotemporal decision-making. We find that all bifurcation points, beyond the very first, fall on a small number of "bifurcation curves". It is the spatial organization of these curves that is shown to be key to determining the shape of the trajectories, such as self-similar or space filling, exhibited during decision-making, irrespective of the trajectory's starting point. Furthermore, we find that a non-Euclidean representation of space considerably reduces the number of bifurcation points in many geometrical configurations, preventing endless indecision and promoting effective spatial decision-making. This suggests that a non-Euclidean neural representation of space may be expected to have evolved across species in order to facilitate spatial decision-making., Comment: 19 pages, 10 figures

Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels or highly curved protrusions of other cells. Recent \textit{in-vitro} experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed ``curvotaxis". The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a ``minimal cell" model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behaviour of this model on different types of curved substrates (sinusoidal, cylinder and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.

While moving, animals must frequently make decisions about their future travel direction, whether they are alone or in a group. Here we investigate this process for zebrafish (Danio rerio), which naturally move in cohesive groups. Employing state-of-the-art virtual reality, we study how real fish follow one or several moving, virtual conspecifics. These data are used to inform, and test, a model of social response that includes a process of explicit decision-making, whereby the fish can decide which of the virtual conspecifics to follow, or to follow some average direction. This approach is in contrast with previous models where the direction of motion was based on a continuous computation, such as directional averaging. Building upon a simplified version of this model [Sridhar et al. 2021], which was limited to a one-dimensional projection of the fish motion, we present here a model that describes the motion of the real fish as it swims freely in two-dimensions. Motivated by experimental observations, the swim speed of the fish in this model uses a burst-and-coast swimming pattern, with the burst frequency being dependent on the distance of the fish from the followed conspecific(s). We demonstrate that this model is able to explain the observed spatial distribution of the real fish behind the virtual conspecifics in the experiments. In particular, the model naturally explains the observed critical bifurcations for a freely swimming fish, whenever the fish makes a decision to follow only one of the virtual conspecifics, instead of following them as an averaged group. This model can provide the foundation for modeling a cohesive shoal of swimming fish, while explicitly describing their directional decision-making process at the individual level, Comment: 32 pages,22 figures (6 in the main text), supplementary material link https://drive.google.com/drive/folders/1H76yOawtv9zuou84VY2HrxOjO-2jXu-w?usp=sharing

Eukaryotic cells intrinsically change their shape, by changing the composition of their membrane and by restructuring their underlying cytoskeleton. We present here further studies and extensions of a minimal physical model, describing a closed vesicle with mobile curved membrane protein complexes. The cytoskeletal forces describe the protrusive force due to actin polymerization which is recruited to the membrane by the curved protein complexes. We characterize the phase diagrams of this model, as function of the magnitude of the active forces, nearest-neighbor protein interactions and the proteins' spontaneous curvature. It was previously shown that this model can explain the formation of lamellipodia-like flat protrusions, and here we explore the regimes where the model can also give rise to filopodia-like tubular protrusions. We extend the simulation with curved components of both convex and concave species, where we find the formation of complex ruffled clusters, as well as internalized invaginations that resemble the process of endocytosis and macropinocytosis. We alter the force model representing the cytoskeleton to simulate the effects of bundled instead of branched structure, resulting in shapes which resemble filopodia., Comment: 28 pages, 15 figure; Supplementary information is available in https://weizmann.box.com/s/5z6aexxk1lmne0b29sf25o451unnj85x (PDF links might be broken). Submitted to Frontiers in Molecular Biosciences and cellular biochemistry special issue "Exploring the Molecular Interplay between the Plasma Membrane and Cytoskeleton during Signal Transduction"

We present a general theoretical model for the spatio-temporal dynamics of animal contests. Inspired by interactions between physical particles, the model is formulated in terms of effective interaction potentials, which map typical elements of contest behaviour into empirically verifiable rules of contestant motion. This allows us to simulate the observable dynamics of contests in various realistic scenarios, notably in dyadic contests over a localized resource. Assessment strategies previously formulated in game-theoretic models, as well as the effects of fighting costs, can be described as variations in our model's parameters. Furthermore, the trends of contest duration associated with these assessment strategies can be derived and understood within the model. Detailed description of the contestants' motion enables the exploration of spatio-temporal properties of asymmetric contests, such as the emergence of chase dynamics. Overall, our framework aims to bridge the growing gap between empirical capabilities and theory in this widespread aspect of animal behaviour.

Protrusions at the leading-edge of a cell play an important role in sensing the extracellular cues, during cellular spreading and motility. Recent studies provided indications that these protrusions wrap (coil) around the extra-cellular fibers. The details of this coiling process, and the mechanisms that drive it, are not well understood. We present a combined theoretical and experimental study of the coiling of cellular protrusions on fibers of different geometry. Our theoretical model describes membrane protrusions that are produced by curved membrane proteins that recruit the protrusive forces of actin polymerization, and identifies the role of bending and adhesion energies in orienting the leading-edges of the protrusions along the azimuthal (coiling) direction. Our model predicts that the cell's leading-edge coils on round fibers, but the coiling ceases for a fiber of elliptical (flat) cross-section. These predictions are verified by 3D visualization and quantitation of coiling on suspended fibers using Dual-View light-sheet microscopy (diSPIM). Overall, we provide a theoretical framework supported by high spatiotemporal resolution experiments capable of resolving coiling of cellular protrusions around extracellular fibers of varying diameters., Comment: 21 pages, 14 figures

Phagocytosis is the process of engulfment and internalization of comparatively large particles by the cell, that plays a central role in the functioning of our immune system. We study the process of phagocytosis by considering a simplified coarse grained model of a three-dimensional vesicle, having uniform adhesion interaction with a rigid particle, in the presence of curved membrane proteins and active cytoskeletal forces. Complete engulfment is achieved when the bending energy cost of the vesicle is balanced by the gain in the adhesion energy. The presence of curved (convex) proteins reduces the bending energy cost by self-organizing with higher density at the highly curved leading edge of the engulfing membrane, which forms the circular rim of the phagocytic cup that wraps around the particle. This allows the engulfment to occur at much smaller adhesion strength. When the curved proteins exert outwards protrusive forces, representing actin polymerization, at the leading edge, we find that engulfment is achieved more quickly and at lower protein density. We consider spherical as well as non-spherical particles, and find that non-spherical particles are more difficult to engulf in comparison to the spherical particles of the same surface area. For non-spherical particles, the engulfment time crucially depends upon the initial orientation of the particles with respect to the vesicle. Our model offers a mechanism for the spontaneous self-organization of the actin cytoskeleton at the phagocytic cup, in good agreement with recent high-resolution experimental observations., Comment: 27 pages, 23 figures

Collective motion by animal groups is affected by internal interactions, external constraints and the influx of information. A quantitative understanding of how these different factors give rise to different modes of collective motion is, at present, lacking.} Here, we study how ants that cooperatively transport a large food item react to an obstacle blocking their path. Combining experiments with a statistical physics model of mechanically coupled active agents, we show that the constraint induces a deterministic collective oscillatory mode that facilitates obstacle circumvention. We provide direct experimental evidence, backed by theory, that this motion is an emergent group effect that does not require any behavioral changes at the individual level. We trace these relaxation oscillations to the interplay between two forces; informed ants pull the load towards the nest while uninformed ants contribute to the motion's persistence along the tangential direction. The model's predictions that oscillations appear above a critical system size, that the group can spontaneously transition into its ordered phase, and that the system can exhibit complete rotations are all verified experimentally. We expect that similar oscillatory modes emerge in collective motion scenarios where the structure of the environment imposes conflicts between individually held information and the group's tendency for cohesiveness.

Dense active matter, in the fluid or amorphous-solid form, has generated intense interest as a model for the dynamics inside living cells and multicellular systems. An extension of the random first-order transition theory (RFOT) to include activity was developed, whereby the activity of the individual particles was added to the free energy of the system in the form of the potential energy of an active particle, trapped by a harmonic potential that describes the effective confinement by the surrounding medium. This active-RFOT model was shown to successfully account for the dependence of the structural relaxation time in the active glass, extracted from simulations, as a function of the activity parameters: the magnitude of the active force ($f_0$) and its persistence time ($\tau_p$). However, significant deviations were found in the limit of large activity (large $f_0$ and/or $\tau_p$). Here we extend the active-RFOT model to high activity using an activity-dependent harmonic confining potential, which we solve self-consistently. The extended model predicts qualitative changes in the high activity regime, which agree with the results of simulations in both three-dimensional and two-dimensional models of active glass.

Eukaryotic cells adhere to extracellular matrix during the normal development of the organism, forming static adhesion as well as during cell motility. We study this process by considering a simplified coarse-grained model of a vesicle that has uniform adhesion energy with a flat substrate, mobile curved membrane proteins and active forces. We find that a high concentration of curved proteins alone increases the spreading of the vesicle, by the self-organization of the curved proteins at the high curvature vesicle-substrate contact line, thereby reducing the bending energy penalty at the vesicle rim. This is most significant in the regime of low bare vesicle-substrate adhesion. When these curved proteins induce protrusive forces, representing the actin cytoskeleton, we find efficient spreading, in the form of sheet-like lamellipodia. Finally, the same mechanism of spreading is found to include a minimal set of ingredients needed to give rise to motile phenotypes., Comment: 30 pages, 27 figures

In swarms of flying insects, the motions of individuals are largely uncoordinated with those of their neighbors, unlike the highly ordered motion of bird flocks. However, it has been observed that insects may transiently form pairs with synchronized relative motion while moving through the swarm. The origin of this phenomenon remains an open question. In particular, it is not known if pairing is a new behavioral process or whether it is a natural byproduct of typical swarming behavior. Here, using an "adaptive-gravity" model that proposes that insects interact via long-range gravity-like acoustic attractions that are modulated by the total background sound (via "adaptivity" or fold-change detection) and that reproduces measured features of real swarms, we show that pair formation can indeed occur without the introduction of additional behavioral rules. In the model, pairs form robustly whenever two insects happen to move together from the center of the swarm (where the background sound is high) toward the swarm periphery (where the background sound is low). Due to adaptivity, the attraction between the pair increases as the background sound decreases, thereby forming a bound state since their relative kinetic energy is smaller than their pair-potential energy. When the pair moves into regions of high background sound, however, the process is reversed and the pair may break up. Our results suggest that pairing should appear generally in biological systems with long-range attraction and adaptive sensing, such as during chemotaxis-driven cellular swarming.

During the last decade, intracellular actin waves have attracted much attention due to their essential role in various cellular functions, ranging from motility to cytokinesis. Experimental methods have advanced significantly and can capture the dynamics of actin waves over a large range of spatio-temporal scales. However, the corresponding coarse-grained theory mostly avoids the full complexity of this multi-scale phenomenon. In this perspective, we focus on a minimal continuum model of activator-inhibitor type and highlight the qualitative role of mass-conservation, which is typically overlooked. Specifically, our interest is to connect between the mathematical mechanisms of pattern formation in the presence of a large-scale mode, due to mass-conservation, and distinct behaviors of actin waves., Comment: 13 pages, 4 figures

During migration cells exhibit a rich variety of seemingly random migration patterns, which makes unraveling the underlying mechanisms that control cell migration a daunting challenge. For efficient migration cells require a mechanism for polarization, so that traction forces are produced in the direction of motion, while adhesion is released to allow forward migration. To simplify the study of this process cells have been studied when placed along one-dimensional tracks, where single cells exhibit both smooth and stick-slip migration modes. The stick-slip motility mode is characterized by protrusive motion at the cell front, coupled with slow cell elongation, which is followed by rapid retractions of the cell back. In this study, we explore a minimal physical model that couples the force applied on the adhesion bonds to the length variations of the cell and the traction forces applied by the polarized actin retrograde flow. We show that the rich spectrum of cell migration patterns emerges from this model as different \emph{deterministic} dynamical phases. This result suggests a source for the large cell-to-cell variability (CCV) in cell migration patterns observed in single cells over time and within cell populations. The large heterogeneity can arise from small fluctuations in the cellular components that are greatly amplified due to moving the cells' internal state across the dynamical phase transition lines. Temporal noise is shown to drive random changes in the cellular polarization direction, which is enhanced during the stick-slip migration mode. These results offer a new framework to explain experimental observations of migrating cells, resulting from noisy switching between underlying deterministic migration modes., Comment: 24 pages, 27 figures

Previous work has suggested that disordered swarms of flying insects can be well modeled as self-gravitating systems, as long as the "gravitational" interaction is adaptive. Motivated by this work we compare the predictions of the classic, mean-field King model for isothermal globular clusters to observations of insect swarms. Detailed numerical simulations of regular and adaptive gravity allow us to expose the features of the swarms' density profiles that are captured by the King model phenomenology, and those that are due to adaptivity and short-range repulsion. Our results provide further support for adaptive gravity as a model for swarms.

The dynamics of active particles is of interest at many levels and is the focus of theoretical and experimental research. There have been many attempts to describe the dynamics of particles affected by random active forces in terms of an effective temperature. This kind of description is tempting due to the similarities (or lack thereof) with systems in or near thermal equilibrium. However, the generality and validity of the effective temperature is not yet fully understood. Here, we studied the dynamics of trapped particles subjected to both thermal and active forces. The particles were not overdamped. Expressions for the effective temperature due to the potential and kinetic energies were derived, and they differ from each other. A third possible effective temperature can be derived from the escape time of the particle from the trap, using a Kramers-like expression for the mean escape time. We found that over a large fraction of the parameter space, the potential energy effective temperature is in agreement with the escape temperature, while the kinetic effective temperature only agrees with the former two in the overdamped limit. Moreover, we show that the specific implementation of the random active force, and not only its first two moments and the two point auto-correlation function, affects the escape time distribution.

Excitable pulses are among the most widespread dynamical patterns that occur in many different systems, ranging from biological cells to chemical reactions and ecological populations. Traditionally, the mutual annihilation of two colliding pulses is regarded as their prototypical signature. Here we show that colliding excitable pulses may exhibit soliton-like crossover and pulse nucleation if the system obeys a mass conservation constraint. In contrast to previous observations in systems without mass conservation, these alternative collision scenarios are robustly observed over a wide range of parameters. We demonstrate our findings using a model of intracellular actin waves since, on time scales of wave propagations over the cell scale, cells obey the conservation of actin monomers. The results provide a key concept to understand the ubiquitous occurrence of actin waves in cells, suggesting why they are so common, and why their dynamics is robust and long-lived., Comment: 6 pages, 2 figures

We study a model for the motion of a tracer particle inside an active gel, exposing the properties of the van Hove distribution of the particle displacements. Active events of a typical force magnitude give rise to non-Gaussian distributions, having exponential tails or side-peaks. The side-peaks appear when the local bulk elasticity of the gel is large enough and few active sources are dominant. We explain the regimes of the different distributions, and study the structure of the peaks for active sources that are susceptible to the elastic stress that they cause inside the gel. We show how the van Hove distribution is altered by both the duty cycle of the active sources and their susceptibility, and suggest it as a sensitive probe to analyze microrheology data in active systems with restoring elastic forces., Comment: 4 pages, 4 figures and supplemental information (5 pages, 4 figures)

The dynamics within active fluids, driven by internal activity of the self-propelled particles, is a subject of intense study in non-equilibrium physics. These systems have been explored using simulations, where the motion of a passive tracer particle is followed. Similar studies have been carried out for passive granular matter that is driven by shearing its boundaries. In both types of systems the non-equilibrium motion have been quantified by defining a set of "effective temperatures", using both the tracer particle kinetic energy and the fluctuation-dissipation relation. We demonstrate that these effective temperatures extracted from the many-body simulations fit analytical expressions that are obtained for a single active particle inside a visco-elastic fluid. This result provides testable predictions and suggests a unified description for the dynamics inside active systems.

Cell shape is determined by a balance of intrinsic properties of the cell as well as its mechanochemical environment. Inhomogeneous shape changes underly many morphogenetic events and involve spatial gradients in active cellular forces induced by complex chemical signaling. Here, we introduce a mechanochemical model based on the notion that cell shape changes may be induced by external diffusible biomolecules that influence cellular contractility (or equivalently, adhesions) in a concentration-dependent manner -- and whose spatial profile in turn is affected by cell shape. We map out theoretically the possible interplay between chemical concentration and cellular structure. Besides providing a direct route to spatial gradients in cell shape profiles in tissues, our results indicate that the dependence on cell shape helps create robust mechanochemical gradients., Comment: 10 pages, 4 figures, Supplementary: 5 pages, 5 figures

We study the force that non-interacting point-like active particles apply to a symmetric inert object in the presence of a gradient of activity and particle sources and sinks. We consider two simple patterns of sources and sinks that are common in biological systems. We analytically solve a one dimensional model designed to emulate higher dimensional systems, and study a two dimensional model by numerical simulations. We specify when the particle flux due to the creation and annihilation of particles can act to smooth the density profile that is induced by a gradient in the velocity of the active particles, and find the net resultant force due to both the gradient in activity and the particle flux. These results are compared qualitatively to observations of nuclear motion inside the oocyte, that is driven by a gradient in activity of actin-coated vesicles., Comment: 14 pages, 8 figures

The physics of active systems of self-propelled particles, in the regime of a dense liquid state, is an open puzzle of great current interest, both for statistical physics and because such systems appear in many biological contexts. We develop a nonequilibrium mode-coupling theory (MCT) for such systems, where activity is included as a colored noise with the particles having a self-propulsion foce $f_0$ and persistence time $\tau_p$. Using the extended MCT and a generalized fluctuation-dissipation theorem, we calculate the effective temperature $T_{eff}$ of the active fluid. The nonequilibrium nature of the systems is manifested through a time-dependent $T_{eff}$ that approaches a constant in the long-time limit, which depends on the activity parameters $f_0$ and $\tau_p$. We find, phenomenologically, that this long-time limit is captured by the potential energy of a single, trapped active particle (STAP). Through a scaling analysis close to the MCT glass transition point, we show that $\tau_\alpha$, the $\alpha$-relaxation time, behaves as $\tau_\alpha\sim f_0^{-2\gamma}$, where $\gamma=1.74$ is the MCT exponent for the passive system. $\tau_\alpha$ may increase or decrease as a function of $\tau_p$ depending on the type of active force correlations, but the behavior is always governed by the same value of the exponent $\gamma$. Comparison with numerical solution of the nonequilibrium MCT as well as simulation results give excellent agreement with the scaling analysis.

We show how a gradient in the motility properties of non-interacting point-like active particles can cause a pressure gradient that pushes a large inert object. We calculate the force on an object inside a system of active particles with position dependent motion parameters, in one and two dimensions, and show that a modified Archimedes' principle is satisfied. We characterize the system, both in terms of the model parameters and in terms of experimentally measurable quantities: the spatial profiles of the density, velocity and pressure. This theoretical analysis is motivated by recent experiments, which showed that the nucleus of a mouse oocyte (immature egg cell) moves from the cortex to the center due to a gradient of activity of vesicles propelled by molecular motors; it more generally applies to artificial systems of controlled localized activity., Comment: 16 pages, 9 figures

Sensory mechanisms in biology, from cells to humans, have the property of adaptivity, whereby the response produced by the sensor is adapted to the overall amplitude of the signal; reducing the sensitivity in the presence of strong stimulus, while increasing it when it is weak. This property is inherently energy consuming and a manifestation of the non-equilibrium nature of living organisms. We explore here how adaptivity affects the effective forces that organisms feel due to others in the context of a uniform swarm, both in two and three dimensions. The interactions between the individuals are taken to be attractive and long-range, of power-law form. We find that the effects of adaptivity inside the swarm are dramatic, where the effective forces decrease (or remain constant) with increasing swarm density. Linear stability analysis demonstrates how this property prevents collapse (Jeans instability), when the forces are adaptive. Adaptivity therefore endows swarms with a natural mechanism for self-stabilization., Comment: 11 pages, 6 figures

How does nonequilibrium activity modify the approach to a glass? This is an important question, since many experiments reveal the near-glassy nature of the cell interior, remodelled by activity. However, different simulations of dense assemblies of active particles, parametrised by a self-propulsion force, $f_0$, and persistence time, $\tau_p$, appear to make contradictory predictions about the influence of activity on characteristic features of glass, such as fragility. This calls for a broad conceptual framework to understand active glasses; here we extend the Random First-Order Transition (RFOT) theory to a dense assembly of self-propelled particles. We compute the active contribution to the configurational entropy using an effective medium approach - that of a single particle in a caging-potential. This simple active extension of RFOT provides excellent quantitative fits to existing simulation results. We find that whereas $f_0$ always inhibits glassiness, the effect of $\tau_p$ is more subtle and depends on the microscopic details of activity. In doing so, the theory automatically resolves the apparent contradiction between the simulation models. The theory also makes several testable predictions, which we verify by both existing and new simulation data, and should be viewed as a step towards a more rigorous analytical treatment of active glass.

Living organisms are inherently out-of-equilibrium systems. We employ new developments in stochastic energetics and rely on a minimal microscopic model to predict the amount of mechanical energy dissipated by such dynamics. Our model includes complex rheological effects and nonequilibrium stochastic forces. By performing active microrheology and tracking micron-sized vesicles in the cytoplasm of living oocytes, we provide unprecedented measurements of the spectrum of dissipated energy. We show that our model is fully consistent with the experimental data, and we use it to offer predictions for the injection and dissipation energy scales involved in active fluctuations., Comment: 5 pages, 2 figures

Active diffusion of intracellular components is emerging as an important process in cell biology. This process is mediated by complex assemblies of molecular motors and cytoskeletal filaments that drive force generation in the cytoplasm and facilitate enhanced motion. The kinetics of molecular motors have been precisely characterized in-vitro by single molecule approaches, however, their in-vivo behavior remains elusive. Here, we study the active diffusion of vesicles in mouse oocytes, where this process plays a key role in nuclear positioning during development, and combine an experimental and theoretical framework to extract molecular-scale force kinetics (force, power-stroke, and velocity) of the in-vivo active process. Assuming a single dominant process, we find that the nonequilibrium activity induces rapid kicks of duration $\tau \sim$ 300 $\mu$s resulting in an average force of $F \sim$ 0.4 pN on vesicles in in-vivo oocytes, remarkably similar to the kinetics of in-vitro myosin-V. Our results reveal that measuring in-vivo active fluctuations allows extraction of the molecular-scale activity in agreement with single-molecule studies and demonstrates a mesoscopic framework to access force kinetics., Comment: 20 pages, 4 figures, see ancillary files for Supplementary Materials, * equally contributing authors

The collective motion of groups of animals emerges from the net effect of the interactions between individual members of the group. In many cases, such as birds, fish, or ungulates, these interactions are mediated by sensory stimuli that predominantly arise from nearby neighbors. But not all stimuli in animal groups are short range. Here, we consider mating swarms of midges, which interact primarily via long-range acoustic stimuli. We exploit the similarity in form between the decay of acoustic and gravitational sources to build a model for swarm behavior. By accounting for the adaptive nature of the midges' acoustic sensing, we show that our "adaptive gravity" model makes mean-field predictions that agree well with experimental observations of laboratory swarms. Our results highlight the role of sensory mechanisms and interaction range in collective animal behavior. The adaptive interactions that we present here open a new class of equations of motion, which may appear in other biological contexts., Comment: 25 pages, 15 figures

Membrane deformation inside living cells is crucial for the proper shaping of various intracellular organelles and is necessary during the fission/fusion processes that allow membrane recycling and transport (e.g. endocytosis). Proteins that induce membrane curvature play a key role in such processes, mostly by adsorbing to the membrane and forming a scaffold that deforms the membrane according to the curvature of the proteins. In this paper we explore the possibility of membrane tube destabilisation through a pearling mechanism enabled by the combined effects of the adsorbed curved proteins and the actin polymerization they may recruit. The pearling instability can furthermore serve as the initiation for fission of the tube into vesicles. We find that adsorbed proteins are more likely to stabilise the tubes, while the actin polymerization can provide the additional constrictive force needed for the robust instability. We discuss the relevance of the theoretical results to in-vivo and in-vitro experiments.