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Directed collective cell migration is central in morphogenesis, wound healing and cancer progression1,2. Although it is well-accepted that the molecular anisotropy of the micro-environment guides this migration3,4, its impact on the pattern of the cell flows remains largely unexplored. Studying confluent human bronchial epithelial cells (HBECs) in vitro, we show that subcellular microgrooves elicit a polar mode of collective migration in millimeter-long bidirectional lanes that are much wider than a cell size, even though cell flows are highly disordered on featureless surfaces 5. This directed flocking-like transition6,7 can be accounted for by a hydrodynamic theory of active polar fluids and corresponding numerical simulations. This model further predicts that anisotropic friction resulting from the grooves lowers the threshold of the transition, which we confirm experimentally. Therefore, microscopic anisotropy of the environment not only directs the collective motion of the cells in the easy direction, but also shapes the cell migration pattern. Flow patterns induced by collective contact guidance are thus markedly different from those induced by supracellular confinement8, demonstrating that all length-scales of the micro-environment must be considered in a comprehensive description of collective migration. Furthermore, artificial microtopographies designed from theoretical considerations can provide a rational strategy to direct cells to specific geometries and functions, which has broad implications, for instance, for tissue engineering strategies in organoid morphogenesis., Comment: Nature Physics, 2024

We construct a hydrodynamic theory of active smectics A in two-dimensional space, including the creation/annihilation and motility of dislocations with Burgers' number $\pm1$. We derive analytical criteria on the set of parameters that lead to flows. We show that the motility of dislocations can lead to flow transitions with distinct features from the previously reported active Helfrich--Hurault shear instability with, notably, a first-order transition in the velocity from quiescence to turbulence., Comment: 5 pages, 5 figures

Several enzymes exhibit enhanced diffusion in the presence of a substrate. One explanation of this enhancement arises from fluctuating dimer models, which suggest that enzymes have a higher diffusion constant when interacting with substrates compared to when they are free. Another possible mechanism, suggested in both experimental and theoretical studies, is that enzymes act as nanoswimmers. However, existing nanoswimmer models have struggled to account for the exceptionally high self-propulsion speeds observed in experiments, with estimated increases in diffusion due to self-propulsion found to be minimal. In this study, we model enzymes as dimers with fluctuating mobility. We show that even dimers can exhibit run-and-tumble motion when transitioning between states of varying mobility within the enzymatic cycle. By exploring a three-state enzymatic cycle, we identify the conditions under which self-propulsion speeds and increases in diffusion rate consistent with experimental observations can be achieved.

We compare three different setups for measuring cell-cell adhesion. We show that the measured strength depends on the type of setup that is used. For identical cells different assays measure different detachment forces. This can be understood from the fact that cell-cell detachment is a global property of the system. We also analyse the role of external force and line tension on contact angle and cell-cell detachment. Comparison with experiment suggests that the current data are essentially dynamical in nature. We dedicate this article to Fyl Pincus who for many of us is an example to be followed not only for outstanding science but also for a marvelous human behavior., Comment: 7 pages, 5 figures

Cell adhesion proteins typically form stable clusters that anchor the cell membrane to its environment. Several works have suggested that cell membrane protein clusters can emerge from a local feedback between the membrane curvature and the density of proteins. Here, we investigate the effect of such curvature-sensing mechanism in the context of cell adhesion proteins. We show how clustering emerges in an intermediate range of adhesion and curvature-sensing strengths. We identify key differences with the tilt-induced gradient sensing mechanism we previously proposed (Lin et al., arXiv:2307.03670, 2023)., Comment: 13 pages, 7 figures

Cell adhesion proteins are transmembrane proteins that bind cells to their environment. These proteins typically cluster into disk-shaped or linear structures. Here we show that such clustering patterns spontaneously emerge when the protein sense the membrane deformation gradient, for example by reaching a lower-energy conformation when the membrane is tilted relative to the underlying binding substrate. Increasing the strength of the membrane gradient-sensing mechanism first yields isolated disk-shaped clusters and then long linear structures. Our theory is coherent with experimental estimates, suggesting that a tilt-induced clustering mechanism is relevant in the context of cell adhesion proteins., Comment: 6 pages, 3 figures, with SI (ancillary files)

Spatiotemporal coordination of chromatin and subnuclear compartments is crucial for cells. Numerous enzymes act inside nucleus\textemdash some of those transiently link and pass two chromatin segments. Here we study how such an active perturbation affects fluctuating dynamics of an inclusion in the chromatic medium. Using numerical simulations and a versatile effective model, we categorize inclusion dynamics into three distinct modes. The transient-link-and-pass activity speeds up inclusion dynamics by affecting a slow mode related to chromatin remodeling, viz., size and shape of the chromatin meshes.

Fluid pumping and the generation of electric current by living tissues are required during morphogenetic processes and for maintainance of homeostasis. How these flows emerge from active and passive ion transport in cells has been well established. However, the interplay between flow and current generation is not well understood. Here, we study the electro-hydraulic coupling that arises from cell ion pumping. We develop a one-dimensional continuum model of fluid and ion transport across active cell membranes. Solving the Nernst-Planck and Poisson equations in the limit of weak charge imbalance allows us to derive approximate analytical solutions of the model. These approximations, consistent with the numerical results in physiologically relevant regime of parameters, allow us to describe electro-hydraulic activity of cells and tissues in terms of experimentally accessible parameters.

We show that dislocations in active 2d smectics with underlying rotational symmetry are always unbound in the presence of noise, meaning the active smectic phase does not exist for non-zero noise in $d=2$. The active smectic phase can, like equilibrium smectics in 2d, be stabilized by applying rotational symmetry breaking fields; however, even in the presence of such fields, active smectics are still much less stable against noise than equilibrium ones, when the symmetry breaking field(s) are weak., Comment: 23 pages, 3 figures

Cell monolayers are a central model system to tissue biophysics. In vivo, epithelial tissues are curved on the scale of microns, and curvature's role in the onset of spontaneous tissue flows is still not well-understood. Here, we present a hydrodynamic theory for an apical-basal asymmetric active nematic gel on a curved strip. We show that surface curvature qualitatively changes monolayer motion compared to flat space: the resulting flows can be thresholdless, and the transition to motion may change from continuous to discontinuous. Surface curvature, friction and active tractions are all shown to control the flow pattern selected: from simple shear to vortex chains., Comment: 5 pages, 3 figures, 20 supplemental pages, 11 supplemental figures, 2 supplemental movies

We derive a fully covariant theory of the hydrodynamics of nematic and polar active surfaces, subjected to internal and external forces and torques. We study the symmetries of polar and nematic surfaces and find that in addition to 5 different types of in-plane isotropic surfaces, polar and nematic surfaces can be classified into 5 polar, 2 pseudopolar, 5 nematic and 2 pseudonematic types of surfaces. We give examples of physical realisations of the different types of surfaces we have identified. We obtain expressions for the equilibrium tensions, moments, and external forces and torques acting on a passive polar or nematic surface. We calculate the entropy production rate using the framework of thermodynamics close to equilibrium and find constitutive equations for polar and nematic active surfaces with different symmetries. We study the instabilities of a confined flat planar-chiral polar active layer and of a confined deformable polar active surface with broken up-down symmetry.

Spatial organization of chromatin plays a critical role in genome regulation. Various types of affinity mediators and enzymes have been attributed to regulate spatial organization of chromatin from a thermodynamics perspective. However, at the mechanistic level, enzymes act in their unique ways. Here, we construct a polymer physics model following the mechanistic scheme of Topoisomerase-II, an enzyme resolving topological constraints of chromatin, and investigate its role on interphase chromatin organization. Our computer simulations demonstrate Topoisomerase-II's ability to phase separate chromatin into eu- and heterochromatic regions with a characteristic wall-like organization of the euchromatic regions. Exploiting a mean-field framework, we argue that the ability of the euchromatic regions crossing each other due to enzymatic activity of Topoisomerase-II induces this phase separation. Motivated from a recent experimental observation on different structural states of the eu- and the heterochromatic units, we further extend our model to a bidisperse setting and show that the characteristic features of the enzymatic activity driven phase separation survives there. The existence of these characteristic features, even under the non-localized action of the enzyme, highlights the critical role of enzymatic activity in chromatin organization, and points out the importance of further experiments along this line., Comment: 4 figures, 3 supplementary figures

Tissues are characterized by layers of functional units such as cells and extracellular matrix (ECM). Nevertheless, how dynamics at interlayer interfaces help transmit cellular forces in tissues remains overlooked. Here, we investigate a multi-layer system where a layer of epithelial cells is seeded upon an elastic substrate in contact with a hard surface. Our experiments show that, upon a cell extrusion event in the cellular layer, long-range wave propagation emerges in the substrate only when the two substrate layers were weakly attached to each other. We then derive a theoretical model which quantitatively reproduces the wave dynamics and explains how frictional sliding between substrate layers helps propagate cellular forces at a variety of scales, depending on the stiffness, thickness, and slipperiness of the substrate. These results highlight the importance of interfacial friction between layers in transmitting mechanical cues in tissues in vivo., Comment: Main texts: 22 pages, 5 figures, 1 table. Supplementary Information: 21 pages including 5 figures. Movies are not available here

We use a theoretical approach to examine the effect of a radial fluid flow or electric current on the growth and homeostasis of a cell spheroid. Such conditions may be generated by a drain of micrometric diameter. To perform this analysis, we describe the tissue as a continuum. We include active mechanical, electric, and hydraulic components in the tissue material properties. We consider a spherical geometry and study the effect of the drain on the dynamics of the cell aggregate. We show that a steady fluid flow or electric current imposed by the drain could be able to significantly change the spheroid long-time state. In particular, our work suggests that a growing spheroid can systematically be driven to a shrinking state if an appropriate external field is applied. Order-of-magnitude estimates suggest that such fields are of the order of the indigenous ones. Similarities and differences with the case of tumors and embryo development are briefly discussed., Comment: 28 pages, 6 figures

We present a minimal model to study liquid phase separation in a fixed pH ensemble. The model describes a mixture composed of macromolecules that exist in three different charge states and have a tendency to phase separate. We introduce the pH dependence of phase separation by means of a set of reactions describing the protonation and deprotonation of macromolecules, as well as the self-ionisation of water. We use conservation laws to identify the conjugate thermodynamic variables at chemical equilibrium. Using this thermodynamic conjugate variables we perform a Legendre transform which defines the corresponding free energy at fixed pH. We first study the possible phase diagram topologies at the isoelectric point of the macromolecules. We then show how the phase behavior depends on pH by moving away from the isoelectric point. We find that phase diagrams as a function of pH strongly depend on whether oppositely charged macromolecules or neutral macromolecules have a stronger tendency to phase separate. We predict the existence of reentrant behavior as a function of pH. In addition, our model also predicts that the region of phase separation is typically broader at the isoelectric point. This model could account for both, the protein separation observed in yeast cells for pH values close to the isoelectric point of many cytosolic proteins and also for the in vitro experiments of single proteins exhibiting phase separation as a function of pH.

We discuss the physical mechanisms that promote or suppress the nucleation of a fluid-filled lumen inside a cell assembly or a tissue. We discuss lumen formation in a continuum theory of tissue material properties in which the tissue is described as a two-fluid system to account for its permeation by the interstitial fluid, and we include fluid pumping as well as active electric effects. Considering a spherical geometry and a polarized tissue, our work shows that fluid pumping and tissue flexoelectricity play a crucial role in lumen formation. We furthermore explore the large variety of long-time states that are accessible for the cell aggregate and its lumen. Our work reveals a role of the coupling of mechanical, electrical and hydraulic phenomena in tissue lumen formation., Comment: Published version

We calculate the Casimir stresses in a thin layer of active fluid with nematic order. By using a stochastic hydrodynamic approach for an active fluid layer of finite thickness $L$, we generalize the Casimir stress for nematic liquid crystals in thermal equilibrium to active systems. We show that the active Casimir stress differs significantly from its equilibrium counterpart. For contractile activity, the active Casimir stress, although attractive like its equilibrium counterpart, diverges logarithmically as $L$ approaches a threshold of the spontaneous flow instability from below. In contrast, for small extensile activity, it is repulsive, has no divergence at any $L$ and has a scaling with $L$ different from its equilibrium counterpart.

We study the dynamics of a thick polar epithelium subjected to the action of both an electric and a flow field in a planar geometry. We develop a generalized continuum hydrodynamic description and describe the tissue as a two component fluid system. The cells and the interstitial fluid are the two components and we keep all terms allowed by symmetry. In particular we keep track of the cell pumping activity for both solvent flow and electric current and discuss the corresponding orders of magnitude. We study the growth dynamics of tissue slabs, their steady states and obtain the dependence of the cell velocity, net cell division rate, and cell stress on the flow strength and the applied electric field. We find that finite thickness tissue slabs exist only in a restricted region of phase space and that relatively modest electric fields or imposed external flows can induce either proliferation or death., Comment: 18 pages, 12 figures

Simplest extensions of single particle dynamics in momentum conserving active fluid - that of an active suspension of two colloidal particles or a single particle confined by a wall - exhibit strong departures from Boltzmann behavior, resulting in either a breakdown of an effective temperature description or a steady state with nonzero entropy production rate. This is a consequence of hydrodynamic interactions that introduce multiplicative noise in the stochastic description of the particle positions. This results in fluctuation induced interactions that depend on distance as a power law. We find that the dynamics of activated colloids in a passive fluid, with stochastic forcing localized on the particle, is different from that of passive colloids in an active fluctuating fluid.

We theoretically explore fluidization of epithelial tissues by active T1 neighbor exchanges. We show that the geometry of cell-cell junctions encodes important information about the local features of the energy landscape, which we support by an elastic theory of T1 transformations. Using a 3D vertex model, we show that the degree of active noise driving forced cell rearrangements governs the stress-relaxation time-scale of the tissue. We study tissue response to in-plane shear at different time scales. At short time, the tissue behaves as a solid, whereas its long-time fluid behavior can be associated with an effective viscosity which scales with the rate of active T1 transformations. Furthermore, we develop a coarse-grained theory, where we treat the tissue as an active fluid and confirm the results of the vertex model. The impact of cell rearrangements on tissue shape is illustrated by studying axial compression of an epithelial tube.

We investigate the effect of stress fluctuations on the stochastic dynamics of an inclusion embedded in a viscous gel. We show that, in non-equilibrium systems, stress fluctuations give rise to an effective attraction towards the boundaries of the confining domain, which is reminiscent of an active Casimir effect. We apply this generic result to the dynamics of deformations of the cell nucleus and we demonstrate the appearance of a fluctuation maximum at a critical level of activity, in agreement with recent experiments [E. Makhija, D. S. Jokhun, and G. V. Shivashankar, Proc. Natl. Acad. Sci. U.S.A. 113, E32 (2016)]., Comment: 12 pages, 5 figures

We study stochastic dynamics of a point and extended inclusion within a one dimensional confined active viscoelastic gel. We show that the dynamics of a point inclusion can be described by a Langevin equation with a confining potential and multiplicative noise. Using a systematic adiabatic elimination over the fast variables, we arrive at an overdamped equation with a proper definition of the multiplicative noise. To highlight various features and to appeal to different biological contexts, we treat the inclusion in turn as a rigid extended element, an elastic element and a viscoelastic (Kelvin-Voigt) element. The dynamics for the shape and position of the extended inclusion can be described by coupled Langevin equations. Deriving exact expressions for the corresponding steady state probability distributions, we find that the active noise induces an attraction to the edges of the confining domain. In the presence of a competing centering force, we find that the shape of the probability distribution exhibits a sharp transition upon varying the amplitude of the active noise. Our results could help understanding the positioning and deformability of biological inclusions, eg. organelles in cells, or nucleus and cells within tissues., Comment: 16 pages, 9 figures

We study the surface fluctuations of a tissue with a dynamics dictated by cell-rearrangement, cell-division, and cell-death processes. Surface fluctuations are calculated in the homeostatic state, where cell division and cell death equilibrate on average. The obtained fluctuation spectrum can be mapped onto several other spectra such as those characterizing incompressible fluids, compressible Maxwell elastomers, or permeable membranes in appropriate asymptotic regimes. Since cell division and cell death are out-of-equilibrium processes, detailed balance is broken, but a generalized fluctuation-response relation is satisfied in terms of appropriate observables. Our work is a first step toward the description of the out-of-equilibrium fluctuations of the surface of a thick epithelium and its dynamical response to external perturbations., Comment: Letter and Supplemental Material

Using active gel theory we study theoretically the properties of the cortical actin layer of animal cells. The cortical layer is described as a non-equilibrium wetting film on the cell membrane. The actin density is approximately constant in the layer and jumps to zero at its edge. The layer thickness is determined by the ratio of the polymerization velocity and the depolymerization rate of actin., Comment: submitted to Eur Phys Jour E

We study theoretically the shapes of biological tubes affected by various pathologies. When epithelial cells grow at an uncontrolled rate, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated : varicose, enlarged, sinusoidal or sausage-like, all of which are found in pathologies of tracheal, renal tubes or arteries. The final shape depends crucially on the mechanical parameters of the tissues : Young modulus, wall-to-lumen ratio, homeostatic pressure. We argue that since tissues must be in quasistatic mechanical equilibrium, abnormal shapes convey information as to what causes the pathology. We calculate a phase diagram of tubular instabilities which could be a helpful guide for investigating the underlying genetic regulation.

We study theoretically the shapes of a dividing epithelial monolayer of cells lying on top of an elastic stroma. The negative tension created by cell division provokes a buckling instability at a finite wave vector leading to the formation of periodic arrays of villi and crypts. The instability is similar to the buckling of a metallic plate under compression. We use the results to rationalize the various structures of the intestinal lining observed \emph{in vivo}. Taking into account the coupling between cell division and local curvature, we obtain different patterns of villi and crypts, which could explain the different morphologies of the small intestine and the colon., Comment: 4 pages, 4 figures

The precise role of the microenvironment on tumor growth is poorly understood. Whereas the tumor is in constant competition with the surrounding tissue, little is known about the mechanics of this interaction. Using a novel experimental procedure, we study quantitatively the effect of an applied mechanical stress on the long-term growth of a spheroid cell aggregate. We observe that a stress of 10 kPa is sufficient to drastically reduce growth by inhibition of cell proliferation mainly in the core of the spheroid. We compare the results to a simple numerical model developed to describe the role of mechanics in cancer progression., Comment: 5 pages, 4 figures

Treating the epithelium as an incompressible fluid adjacent to a viscoelastic stroma, we find a novel hydrodynamic instability that leads to the formation of protrusions of the epithelium into the stroma. This instability is a candidate for epithelial fingering observed in vivo. It occurs for sufficiently large viscosity, cell-division rate and thickness of the dividing region in the epithelium. Our work provides physical insight into a potential mechanism by which interfaces between epithelia and stromas undulate, and potentially by which tissue dysplasia leads to cancerous invasion., Comment: 4 pages, 3 figures

Eukaryotic cells and intracellular pathogens such as bacteria or viruses utilize the actin polymerization machinery to propel themselves forward. Thereby, the onset of motion and choice of direction may be the result of a spontaneous symmetry-breaking or might be triggered by external signals and preexisting asymmetries, e.g. through a previous septation in bacteria. Although very complex, a key feature of cellular motility is the ability of actin to form dense polymeric networks, whose microstructure is tightly regulated by the cell. These polar actin networks produce the forces necessary for propulsion but may also be at the origin of a spontaneous symmetry-breaking. Understanding the exact role of actin dynamics in cell motility requires multiscale approaches which capture at the same time the polymer network structure and dynamics on the scale of a few nanometers and the macroscopic distribution of elastic stresses on the scale of the whole cell. In this chapter we review a selection of theories on how mechanical material properties and growth processes interact to induce the onset of actin based motion., Comment: 16 pages, 14 figures, chapter in book "Cell mechanics: from single scale-based models to multiscale modelling"

We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal layers, suggests a mechanism underlying the seed and soil hypothesis introduced by Stephen Paget in 1889 and yields realistic values for metastatic inefficiency. We propose a number of key experiments to test these concepts. The homeostatic pressure as introduced in this work could constitute a quantitative, experimentally accessible measure for the metastatic potential of early malignant growths., Comment: 13 pages, 11 figures, to be published in the HFSP Journal

We show that the synchronization transition of a large number of noisy coupled oscillators is an example for a dynamic critical point far from thermodynamic equilibrium. The universal behaviors of such critical oscillators, arranged on a lattice in a $d$-dimensional space and coupled by nearest neighbors interactions, can be studied using field theoretical methods. The field theory associated with the critical point of a homogeneous oscillatory instability (or Hopf bifurcation of coupled oscillators) is the complex Ginzburg-Landau equation with additive noise. We perform a perturbative renormalization group (RG) study in a $4-\epsilon$ dimensional space. We develop an RG scheme that eliminates the phase and frequency of the oscillations using a scale-dependent oscillating reference frame. Within a Callan-Symanzik RG scheme to two-loop order in perturbation theory, we find that the RG fixed point is formally related to the one of the model $A$ dynamics of the real Ginzburg-Landau theory with an O(2) symmetry of the order parameter. Therefore, the dominant critical exponents for coupled oscillators are the same as for this equilibrium field theory. This formal connection with an equilibrium critical point imposes a relation between the correlation and response functions of coupled oscillators in the critical regime. Since the system operates far from thermodynamic equilibrium, a strong violation of the fluctuation-dissipation relation occurs and is characterized by a universal divergence of an effective temperature. The formal relation between critical oscillators and equilibrium critical points suggests that long-range phase order exists in critical oscillators above two dimensions., Comment: 24 pages, published in 2005

We discuss the motion of colloidal particles relative to a two component fluid consisting of solvent and solute. Particle motion can result from (i) net body forces on the particle due to external fields such as gravity; (ii) slip velocities on the particle surface due to surface dissipative phenomena. The perturbations of the hydrodynamic flow field exhibits characteristic differences in cases (i) and (ii) which reflect different patterns of momentum flux corresponding to the existence of net forces, force dipoles or force quadrupoles. In the absence of external fields, gradients of concentration or pressure do not generate net forces on a colloidal particle. Such gradients can nevertheless induce relative motion between particle and fluid. We present a generic description of surface dissipative phenomena based on the linear response of surface fluxes driven by conjugate surface forces. In this framework we discuss different transport scenarios including self-propulsion via surface slip that is induced by active processes on the particle surface. We clarify the nature of force balances in such situations., Comment: 22 pages, 1 figure

Dynamin is a ubiquitous GTPase that tubulates lipid bilayers and is implicated in many membrane severing processes in eukaryotic cells. Setting the grounds for a better understanding of this biological function, we develop a generalized hydrodynamics description of the conformational change of large dynamin-membrane tubes taking into account GTP consumption as a free energy source. On observable time scales, dissipation is dominated by an effective dynamin/membrane friction and the deformation field of the tube has a simple diffusive behavior, which could be tested experimentally. A more involved, semi-microscopic model yields complete predictions for the dynamics of the tube and possibly accounts for contradictory experimental results concerning its change of conformation as well as for plectonemic supercoiling., Comment: 17 pages, 4 figures; typos corrected, reference added

We study the universal thermodynamic properties of systems consisting of many coupled oscillators operating in the vicinity of a homogeneous oscillating instability. In the thermodynamic limit, the Hopf bifurcation is a dynamic critical point far from equilibrium described by a statistical field theory. We perform a perturbative renormalization group study, and show that at the critical point a generic relation between correlation and response functions appears. At the same time the fluctuation-dissipation relation is strongly violated., Comment: 10 pages, 1 figure

We develop a general theory for active viscoelastic materials made of polar filaments. This theory is motivated by the dynamics of the cytoskeleton. The continuous consumption of a fuel generates a non equilibrium state characterized by the generation of flows and stresses. Our theory can be applied to experiments in which cytoskeletal patterns are set in motion by active processes such as those which are at work in cells., Comment: 28 pages, 2 figures

We study the motion of oil drops propelled by actin polymerization in cell extracts. Drops deform and acquire a pear-like shape under the action of the elastic stresses exerted by the actin comet. We solve this free boundary problem and calculate the drop shape taking into account the elasticity of the actin gel and the variation of the polymerization velocity with normal stress. The pressure balance on the liquid drop imposes a zero propulsive force if gradients in surface tension or internal pressure are not taken into account. Quantitative parameters of actin polymerization are obtained by fitting theory to experiment., Comment: 5 pages, 4 figures

It has been observed experimentally that the actin gel grown from spherical beads coated with polymerization enzymes spontaneously breaks the symmetry of its spherical shape, and yields a ``comet'' pushing the bead forward. We propose a mechano-chemical coupling mechanism for the initialization of this symmetry breaking. Key assumptions are that the dissociation of the gel takes place mostly in the region of the external surface, and that the rates of the dissociation depends on the tensile stress in the gel. We analyze a simplified two-dimensional model with a circular substrate. Our analysis shows that the symmetric steady state is always unstable against the inhomogeneous modulation of the thickness of the gel layer, for any radius of the circular substrate. We argue that this model represents the essential feature of the three-dimensional systems for a certain range of characteristic lengths of the modulation. The characteristic time of the symmetry breaking process in our model depends linearly on the radius of curvature of the substrate surface, which is consistent with experimental results, using spherical latex beads as substrate. Our analysis of the symmetry breaking phenomenon demonstrates aspects of mechano-chemical couplings that should be working in vivo as well as in vitro., Comment: 21 pages' text and 8 figures

Motivated by the motion of nematode sperm cells, we present a model for the motion of an adhesive gel on a solid substrate. The gel polymerizes at the leading edge and depolymerizes at the rear. The motion results from a competition between a self-generated swelling gradient and the adhesion on the substrate. The resulting stress provokes the rupture of the adhesion points and allows for the motion. The model predicts an unusual force-velocity relation which depends in significant ways on the point of application of the force., Comment: 4 pages, 1 figure

We show that the formation of membrane tubes (or membrane tethers), which is a crucial step in many biological processes, is highly non-trivial and involves first order shape transitions. The force exerted by an emerging tube is a non-monotonic function of its length. We point out that tubes attract each other, which eventually leads to their coalescence. We also show that detached tubes behave like semiflexible filaments with a rather short persistence length. We suggest that these properties play an important role in the formation and structure of tubular organelles., Comment: 4 pages, 3 figures

We introduce the concept of self-tuned criticality as a general mechanism for signal detection in sensory systems. In the case of hearing, we argue that active amplification of faint sounds is provided by a dynamical system which is maintained at the threshold of an oscillatory instability. This concept can account for the exquisite sensitivity of the auditory system and its wide dynamic range, as well as its capacity to respond selectively to different frequencies. A specific model of sound detection by the hair cells of the inner ear is discussed. We show that a collection of motor proteins within a hair bundle can generate oscillations at a frequency which depends on the elastic properties of the bundle. Simple variation of bundle geometry gives rise to hair cells with characteristic frequencies which span the range of audibility. Tension-gated transduction channels, which primarily serve to detect the motion of a hair bundle, also tune each cell by admitting ions which regulate the motor protein activity. By controlling the bundle's propensity to oscillate, this feedback automatically maintains the system in the operating regime where it is most sensitive to sinusoidal stimuli. The model explains how hair cells can detect sounds which carry less energy than the background noise., Comment: 11 pages, 6 figures, REVTEX