arXiv subjects

Ricard Alert

Publications and source records attributed to Ricard Alert.

At least 37 records · Page 2Linked to original sources

arXiv2021

Collective durotaxis of cohesive cell clusters on a stiffness gradient

Many types of motile cells perform durotaxis, namely, directed migration following gradients of substrate stiffness. Recent experiments have revealed that cell monolayers can migrate toward stiffer regions even when individual cells do not -- a phenomenon known as collective durotaxis. Here we address the spontaneous motion of finite cohesive cell monolayers on a stiffness gradient. We theoretically analyze a continuum active polar fluid model that has been tested in recent wetting assays of epithelial tissues, and includes two types of active forces (cell-substrate traction and cell-cell contractility). The competition between the two active forces determines whether a cell monolayer spreads or contracts. Here, we show that this model generically predicts collective durotaxis, and that it features a variety of dynamical regimes as a result of the interplay between the spreading state and the global propagation, including sequential contraction and spreading of the monolayer as it moves toward higher stiffness. We solve the model exactly in some relevant cases, which provides both physical insights into the mechanisms of tissue durotaxis and spreading as well as a variety of predictions that could guide the design of future experiments.

physics.bio-ph↗

arXiv2021

Living cells on the move

Spectacular collective phenomena such as jamming, turbulence, wetting, and waves emerge when living cells migrate in groups.

physics.bio-ph↗

arXiv2021

Topological defects promote layer formation in Myxococcus xanthus colonies

The soil bacterium Myxococcus xanthus lives in densely packed groups that form dynamic three-dimensional patterns in response to environmental changes, such as droplet-like fruiting bodies during starvation. The development of these multicellular structures begins with the sequential formation of cell layers in a process that is poorly understood. Using confocal three-dimensional imaging, we find that motile rod-shaped M. xanthus cells are densely packed and aligned in each layer, forming an active nematic liquid crystal. Cell alignment is nearly perfect throughout the population except at point defects that carry half-integer topological charge. We observe that new cell layers preferentially form at the position of +1/2 defects, whereas holes preferentially open at -1/2 defects. To explain these findings, we model the bacterial colony as an extensile active nematic fluid with anisotropic friction. In agreement with our experimental measurements, this model predicts an influx of cells toward +1/2 defects, and an outflux of cells from -1/2 defects. Our results suggest that cell motility and mechanical cell-cell interactions are sufficient to promote the formation of cell layers at topological defects, thereby seeding fruiting bodies in colonies of M. xanthus.

physics.bio-ph↗

arXiv2021

Active Turbulence

Active fluids exhibit spontaneous flows with complex spatiotemporal structure, which have been observed in bacterial suspensions, sperm cells, cytoskeletal suspensions, self-propelled colloids, and cell tissues. Despite occurring in the absence of inertia, chaotic active flows are reminiscent of inertial turbulence, and hence they are known as active turbulence. Here, we survey the field, providing a unified perspective over different classes of active turbulence. To this end, we divide our review in sections for systems with either polar or nematic order, and with or without momentum conservation (wet/dry). Comparing to inertial turbulence, we highlight the emergence of power-law scaling with either universal or non-universal exponents. We also contrast scenarios for the transition from steady to chaotic flows, and we discuss the absence of energy cascades. We link this feature to both the existence of intrinsic length scales and the self-organized nature of energy injection in active turbulence, which are fundamental differences with inertial turbulence. We close by outlining the emerging picture, remaining challenges, and future directions.

cond-mat.soft↗

arXiv2021

Scaling regimes of active turbulence with external dissipation

Active fluids exhibit complex turbulent-like flows at low Reynolds number. Recent work predicted that 2d active nematic turbulence follows universal scaling laws. However, experimentally testing these predictions is conditioned by the coupling to the 3d environment. Here, we measure the spectrum of the kinetic energy, $E(q)$, in an active nematic film in contact with a passive oil layer. At small and intermediate scales, we find the scaling regimes $E(q)\sim q^{-4}$ and $E(q)\sim q^{-1}$, respectively, in agreement with the theoretical prediction for 2d active nematics. At large scales, however, we find a new scaling $E(q)\sim q$, which emerges when the dissipation is dominated by the 3d oil layer. In addition, we derive an explicit expression for the spectrum that spans all length scales, thus explaining and connecting the different scaling regimes. This allows us to fit the data and extract the length scale that controls the crossover to the new large-scale regime, which we tune by varying the oil viscosity. Overall, our work experimentally demonstrates the emergence of universal scaling laws in active turbulence, and it establishes how the spectrum is affected by external dissipation.

cond-mat.soft↗

arXiv2021

Chemotactic smoothing of collective migration

Collective migration -- the directed, coordinated motion of many self-propelled agents -- is a fascinating emergent behavior exhibited by active matter that has key functional implications for biological systems. Extensive studies have elucidated the different ways in which this phenomenon may arise. Nevertheless, how collective migration can persist when a population is confronted with perturbations, which inevitably arise in complex settings, is poorly understood. Here, by combining experiments and simulations, we describe a mechanism by which collectively migrating populations smooth out large-scale perturbations in their overall morphology, enabling their constituents to continue to migrate together. We focus on the canonical example of chemotactic migration of Escherichia coli, in which fronts of cells move via directed motion, or chemotaxis, in response to a self-generated nutrient gradient. We identify two distinct modes in which chemotaxis influences the morphology of the population: cells in different locations along a front migrate at different velocities due to spatial variations in (i) the local nutrient gradient and in (ii) the ability of cells to sense and respond to the local nutrient gradient. While the first mode is destabilizing, the second mode is stabilizing and dominates, ultimately driving smoothing of the overall population and enabling continued collective migration. This process is autonomous, arising without any external intervention; instead, it is a population-scale consequence of the manner in which individual cells transduce external signals. Our findings thus provide insights to predict, and potentially control, the collective migration and morphology of cell populations and diverse other forms of active matter.

physics.bio-ph↗

arXiv2020

Universal scaling of active nematic turbulence

A landmark of turbulence is the emergence of universal scaling laws, such as Kolmogorov's $E(q)\sim q^{-5/3}$ scaling of the kinetic energy spectrum of inertial turbulence with the wave vector $q$. In recent years, active fluids have been shown to exhibit turbulent-like flows at low Reynolds number. However, the existence of universal scaling properties in these flows has remained unclear. To address this issue, here we propose a minimal defect-free hydrodynamic theory for two-dimensional active nematic fluids at vanishing Reynolds number. By means of large-scale simulations and analytical arguments, we show that the kinetic energy spectrum exhibits a universal scaling $E(q)\sim q^{-1}$ at long wavelengths. We find that the energy injection due to activity has a peak at a characteristic length scale, which is selected by a nonlinear mechanism. In contrast to inertial turbulence, energy is entirely dissipated at the scale where it is injected, thus precluding energy cascades. Nevertheless, the non-local character of the Stokes flow establishes long-ranged velocity correlations, which lead to the scaling behavior. We conclude that active nematic fluids define a distinct universality class of turbulence at low Reynolds number.

cond-mat.soft↗

arXiv2020

Role of Substrate Stiffness in Tissue Spreading: Wetting Transition and Tissue Durotaxis

Living tissues undergo wetting transitions: On a surface, they can either form a droplet-like cell aggregate or spread as a monolayer of migrating cells. Tissue wetting depends not only on the chemical but also on the mechanical properties of the substrate. Here, we study the role of substrate stiffness in tissue spreading, which we describe by means of an active polar fluid model. Taking into account that cells exert larger active traction forces on stiffer substrates, we predict a tissue wetting transition at a critical substrate stiffness that decreases with tissue size. On substrates with a stiffness gradient, we find that the tissue spreads faster on the stiffer side. Further, we show that the tissue can wet the substrate on the stiffer side while dewetting from the softer side. We also show that, by means of viscous forces transmitted across the tissue, the stiffer-side interface can transiently drag the softer-side interface towards increasing stiffness, against its spreading tendency. These two effects result in directed tissue migration up the stiffness gradient. This phenomenon -- tissue durotaxis -- can thus emerge both from dewetting at the soft side and from hydrodynamic interactions between the tissue interfaces. Overall, our work unveils mechanisms whereby substrate stiffness impacts the collective migration and the active wetting properties of living tissues, which are relevant in development, regeneration, and cancer.

physics.bio-ph↗

arXiv2019

Non-uniform growth and surface friction determine bacterial biofilm morphology on soft substrates

During development, organisms acquire three-dimensional shapes with important physiological consequences. While the basic mechanisms underlying morphogenesis are known in eukaryotes, it is often difficult to manipulate them in vivo. To circumvent this issue, here we present a study of developing Vibrio cholerae biofilms grown on agar substrates in which the spatiotemporal morphological patterns were altered by varying the agar concentration. Expanding biofilms are initially flat, but later experience a mechanical instability and become wrinkled. Whereas the peripheral region develops ordered radial stripes, the central region acquires a zigzag herringbone-like wrinkle pattern. Depending on the agar concentration, the wrinkles initially appear either in the peripheral region and propagate inward (low agar concentration) or in the central region and propagate outward (high agar concentration). To understand these experimental observations, we developed a model that considers diffusion of nutrients and their uptake by bacteria, bacterial growth/biofilm matrix production, mechanical deformation of both the biofilm and the agar, and the friction between them. Our model demonstrates that depletion of nutrients beneath the central region of the biofilm results in radially-dependent growth profiles, which in turn, produce anisotropic stresses that dictate the morphology of wrinkles. Furthermore, we predict that increasing surface friction (agar concentration) reduces stress anisotropy and shifts the location of the maximum compressive stress, where the wrinkling instability first occurs, toward the center of the biofilm, in agreement with our experimental observations. Our results are broadly applicable to bacterial biofilms with similar morphologies and also provide insight into how other bacterial biofilms form distinct wrinkle patterns.

physics.bio-ph↗

arXiv2019

Physical Models of Collective Cell Migration

Collective cell migration is a key driver of embryonic development, wound healing, and some types of cancer invasion. Here we provide a physical perspective of the mechanisms underlying collective cell migration. We begin with a catalogue of the cell-cell and cell-substrate interactions that govern cell migration, which we classify into positional and orientational interactions. We then review the physical models that have been developed to explain how these interactions give rise to collective cellular movement. These models span the sub-cellular to the supracellular scales, and they include lattice models, phase fields models, active network models, particle models, and continuum models. For each type of model, we discuss its formulation, its limitations, and the main emergent phenomena that it has successfully explained. These phenomena include flocking and fluid-solid transitions, as well as wetting, fingering, and mechanical waves in spreading epithelial monolayers. We close by outlining remaining challenges and future directions in the physics of collective cell migration.

physics.bio-ph↗

arXiv2019

Active Fingering Instability in Tissue Spreading

During the spreading of epithelial tissues, the advancing tissue front often develops fingerlike protrusions. Their resemblance to traditional viscous fingering patterns in driven fluids suggests that epithelial fingers could arise from an interfacial instability. However, the existence and physical mechanism of such a putative instability remain unclear. Here, based on an active polar fluid model for epithelial spreading, we analytically predict a generic instability of the tissue front. On the one hand, active cellular traction forces impose a velocity gradient that leads to an accelerated front, which is, thus, unstable to long-wavelength perturbations. On the other hand, contractile intercellular stresses typically dominate over surface tension in stabilizing short-wavelength perturbations. Finally, the finite range of hydrodynamic interactions in the tissue selects a wavelength for the fingering pattern, which is, thus, given by the smallest between the tissue size and the hydrodynamic screening length. Overall, we show that spreading epithelia experience an active fingering instability based on a simple kinematic mechanism. Moreover, our results underscore the crucial role of long-range hydrodynamic interactions in the dynamics of tissue morphology.

physics.bio-ph↗

arXiv2019

Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression.

physics.bio-ph↗

arXiv2017

Mixed-order phase transition in a colloidal crystal

Mixed-order phase transitions display a discontinuity in the order parameter like first-order transitions yet feature critical behavior like second-order transitions. Such transitions have been predicted for a broad range of equilibrium and nonequilibrium systems, but their experimental observation has remained elusive. Here, we analytically predict and experimentally realize a mixed-order equilibrium phase transition. Specifically, a discontinuous solid-solid transition in a two-dimensional crystal of paramagnetic colloidal particles is induced by a magnetic field $H$. At the transition field $H_{\text{s}}$, the energy landscape of the system becomes completely flat, which causes diverging fluctuations and correlation length $ξ\propto | H^2 - H_{\text{s}}^2|^{-1/2}$. Mean-field critical exponents are predicted, since the upper critical dimension of the transition is $d_{\text{u}}=2$. Our colloidal system provides an experimental test bed to probe the unconventional properties of mixed-order phase transitions.

cond-mat.stat-mech↗

arXiv2017

Fluidization and Active Thinning by Molecular Kinetics in Active Gels

We derive the constitutive equations of an active polar gel from a model for the dynamics of elastic molecules that link polar elements. Molecular binding kinetics induces the fluidization of the material, giving rise to Maxwell viscoelasticity and, provided that detailed balance is broken, to the generation of active stresses. We give explicit expressions for the transport coefficients of active gels in terms of molecular properties, including nonlinear contributions on the departure from equilibrium. In particular, when activity favors linker unbinding, we predict a decrease of viscosity with activity - active thinning - of kinetic origin, which could explain some experimental results on the cell cortex. By bridging the molecular and hydrodynamic scales, our results could help understand the interplay between molecular perturbations and the mechanics of cells and tissues.

physics.bio-ph↗

arXiv2016

Emergent structures and dynamics of cell colonies by contact inhibition of locomotion

Cells in tissues can organize into a broad spectrum of structures according to their function. Drastic changes of organization, such as epithelial-mesenchymal transitions or the formation of spheroidal aggregates, are often associated either to tissue morphogenesis or to cancer progression. Here, we study the organization of cell colonies by means of simulations of self-propelled particles with generic cell-like interactions. The interplay between cell softness, cell-cell adhesion, and contact inhibition of locomotion (CIL) yields structures and collective dynamics observed in several existing tissue phenotypes. These include regular distributions of cells, dynamic cell clusters, gel-like networks, collectively migrating monolayers, and 3D aggregates. We give analytical predictions for transitions between noncohesive, cohesive, and 3D cell arrangements. We explicitly show how CIL yields an effective repulsion that promotes cell dispersal, thereby hindering the formation of cohesive tissues. Yet, in continuous monolayers, CIL leads to collective cell motion, ensures tensile intercellular stresses, and opposes cell extrusion. Thus, our work highlights the prominent role of CIL in determining the emergent structures and dynamics of cell colonies.

physics.bio-ph↗

arXiv2016

Formation of metastable phases by spinodal decomposition

Metastable phases may be spontaneously formed from other metastable phases through nucleation. Here we demonstrate the spontaneous formation of a metastable phase from an unstable equilibrium by spinodal decomposition, which leads to a transient coexistence of stable and metastable phases. This phenomenon is generic within the recently introduced scenario of the landscape-inversion phase transitions, which we experimentally realize as a structural transition in a colloidal crystal. This transition exhibits a rich repertoire of new phase-ordering phenomena, including the coexistence of two equilibrium phases connected by two physically different interfaces. In addition, this scenario enables the control of sizes and lifetimes of metastable domains. Our findings open a new setting that broadens the fundamental understanding of phase-ordering kinetics, and yield new prospects of applications in materials science.

cond-mat.soft↗

arXiv2016

Bleb Nucleation through Membrane Peeling

We study the nucleation of blebs, i.e., protrusions arising from a local detachment of the membrane from the cortex of a cell. Based on a simple model of elastic linkers with force-dependent kinetics, we show that bleb nucleation is governed by membrane peeling. By this mechanism, the growth or shrinkage of a detached membrane patch is completely determined by the linker kinetics, regardless of the energetic cost of the detachment. We predict the critical nucleation radius for membrane peeling and the corresponding effective energy barrier. These may be typically smaller than those predicted by classical nucleation theory, implying a much faster nucleation. We also perform simulations of a continuum stochastic model of membrane-cortex adhesion to obtain the statistics of bleb nucleation times as a function of the stress on the membrane. The determinant role of membrane peeling changes our understanding of bleb nucleation and opens new directions in the study of blebs.

physics.bio-ph↗

arXiv2016

Model for probing membrane-cortex adhesion by micropipette aspiration and fluctuation spectroscopy

We propose a model for membrane-cortex adhesion which couples membrane deformations, hydrodynamics and kinetics of membrane-cortex ligands. In its simplest form, the model gives explicit predictions for the critical pressure for membrane detachment and for the value of adhesion energy. We show that these quantities exhibit a significant dependence on the active acto-myosin stresses. The model provides a simple framework to access quantitative information on cortical activity by means of micropipette experiments. We also extend the model to incorporate fluctuations and show that detailed information on the stability of membrane-cortex coupling can be obtained by a combination of micropipette aspiration and fluctuation spectroscopy measurements.

physics.bio-ph↗