Approches physiques de problématiques biologiques

Publications de l’équipe

Année de publication : 2015

M Leoni, P Sens (2015 Mar 14)

Polarization of cells and soft objects driven by mechanical interactions: consequences for migration and chemotaxis.

Physical review. E, Statistical, nonlinear, and soft matter physics : 022720 En savoir plus
Résumé

We study a generic model for the polarization and motility of self-propelled soft objects, biological cells, or biomimetic systems, interacting with a viscous substrate. The active forces generated by the cell on the substrate are modeled by means of oscillating force multipoles at the cell-substrate interface. Symmetry breaking and cell polarization for a range of cell sizes naturally « emerge » from long range mechanical interactions between oscillating units, mediated both by the intracellular medium and the substrate. However, the harnessing of cell polarization for motility requires substrate-mediated interactions. Motility can be optimized by adapting the oscillation frequency to the relaxation time of the system or when the substrate and cell viscosities match. Cellular noise can destroy mechanical coordination between force-generating elements within the cell, resulting in sudden changes of polarization. The persistence of the cell’s motion is found to depend on the cell size and the substrate viscosity. Within such a model, chemotactic guidance of cell motion is obtained by directionally modulating the persistence of motion, rather than by modulating the instantaneous cell velocity, in a way that resembles the run and tumble chemotaxis of bacteria.

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Anagha Datar, Thomas Bornschlögl, Patricia Bassereau, Jacques Prost, Pramod A Pullarkat (2015 Feb 5)

Dynamics of membrane tethers reveal novel aspects of cytoskeleton-membrane interactions in axons.

Biophysical journal : 489-97 : DOI : 10.1016/j.bpj.2014.11.3480 En savoir plus
Résumé

Mechanical properties of cell membranes are Known to be Significantly Influenced by the Underlying cortical cytoskeleton. The art of pulling membrane tethers from cells is one of the MOST effective ways of studying the mechanics membrane and the membrane-cortex interaction. In this article, we show That axon membranes make an interesting system to exhibit explores As They Both free membrane-like behavior Where the tether-junction membrane is movable on the area of ​​the axons (Unlike Many –other cell membranes) as well as cell- like behavior Where There are transient and spontaneous eruptions in the strength tether That vanish When F-actin is depolymerized. We analyze the passive and spontaneous responses of axonal membrane tethers and offers theoretical models to explain the Observed behavior.

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Année de publication : 2014

Morgan Delarue, Jean-François Joanny, Frank Jülicher, Jacques Prost (2014 Dec 9)

Stress distributions and cell flows in a growing cell aggregate.

Interface focus : 20140033 : DOI : 10.1098/rsfs.2014.0033 En savoir plus
Résumé

We discuss the short-time response of a multicellular spheroid to an external pressure jump. Our experiments show that 5 min after the pressure jump, the cell density increases in the centre of the spheroid but does not change appreciably close to the surface of the spheroid. This result can be explained if the cells are polarized which we show to be the case. Motivated by the experimental results, we develop a theory for polarized spheroids where the cell polarity is radial (except in a thin shell close to the spheroid surface). The theory takes into account the dependence of cell division and apoptosis rates on the local stress, the cell polarity and active stress generated by the cells and the dependence of active stress on the local pressure. We find a short-time increase of the cell density after a pressure jump that decays as a power law from the spheroid centre, which is in reasonable agreement with the experimental results. By comparing our theory to experiments, we can estimate the isotropic compression modulus of the tissue.

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Philippe Bun, JunJun Liu, Hervé Turlier, ZengZhen Liu, Karen Uriot, Jean-François Joanny, Maïté Coppey-Moisan (2014 Jul 17)

Mechanical checkpoint for persistent cell polarization in adhesion-naive fibroblasts.

Biophysical journal : 324-35 : DOI : 10.1016/j.bpj.2014.05.041 En savoir plus
Résumé

Cell polarization is a fundamental biological process implicated in nearly every aspect of multicellular development. The role of cell-extracellular matrix contacts in the establishment and the orientation of cell polarity have been extensively studied. However, the respective contributions of substrate mechanics and biochemistry remain unclear. Here we propose a believed novel single-cell approach to assess the minimal polarization trigger. Using nonadhered round fibroblast cells, we show that stiffness sensing through single localized integrin-mediated cues are necessary and sufficient to trigger and direct a shape polarization. In addition, the traction force developed by cells has to reach a minimal threshold of 56 ± 1.6 pN for persistent polarization. The polarization kinetics increases with the stiffness of the cue. The polarized state is characterized by cortical actomyosin redistribution together with cell shape change. We develop a physical model supporting the idea that a local and persistent inhibition of actin polymerization and/or myosin activity is sufficient to trigger and sustain the polarized state. Finally, the cortical polarity propagates to an intracellular polarity, evidenced by the reorientation of the centrosome. Our results define the minimal adhesive requirements and quantify the mechanical checkpoint for persistent cell shape and organelle polarization, which are critical regulators of tissue and cell development.

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C Blanch-Mercader, J Casademunt, J F Joanny (2014 May 24)

Morphology and growth of polarized tissues.

The European physical journal. E, Soft matter : 41 : DOI : 10.1140/epje/i2014-14041-2 En savoir plus
Résumé

We study and classify the time-dependent morphologies of polarized tissues subject to anisotropic but spatially homogeneous growth. Extending previous studies, we model the tissue as a fluid, and discuss the interplay of the active stresses generated by the anisotropic cell division and three types of passive mechanical forces: viscous stresses, friction with the environment and tension at the tissue boundary. The morphology dynamics is formulated as a free-boundary problem, and conformal mapping techniques are used to solve the evolution numerically. We combine analytical and numerical results to elucidate how the different passive forces compete with the active stresses to shape the tissue in different temporal regimes and derive the corresponding scaling laws. We show that in general the aspect ratio of elongated tissues is non-monotonic in time, eventually recovering isotropic shapes in the presence of friction forces, which are asymptotically dominant.

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Philippe Marcq (2014 Apr 29)

Spatio-temporal dynamics of an active, polar, viscoelastic ring.

The European physical journal. E, Soft matter : 29 : DOI : 10.1140/epje/i2014-14029-x En savoir plus
Résumé

Constitutive equations for a one-dimensional, active, polar, viscoelastic liquid are derived by treating the strain field as a slow hydrodynamic variable. Taking into account the couplings between strain and polarity allowed by symmetry, the hydrodynamics of an active, polar, viscoelastic body include an evolution equation for the polarity field that generalizes the damped Kuramoto-Sivashinsky equation. Beyond thresholds of the active coupling coefficients between the polarity and the stress or the strain rate, bifurcations of the homogeneous state lead first to stationary waves, then to propagating waves of the strain, stress and polarity fields. I argue that these results are relevant to living matter, and may explain rotating actomyosin rings in cells and mechanical waves in epithelial cell monolayers.

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Morgan Delarue, Fabien Montel, Danijela Vignjevic, Jacques Prost, Jean-François Joanny, Giovanni Cappello (2014 Apr 2)

Compressive stress inhibits proliferation in tumor spheroids through a volume limitation.

Biophysical journal : 1821-8 : DOI : 10.1016/j.bpj.2014.08.031 En savoir plus
Résumé

In most instances, the growth of solid tumors occurs in constrained environments and requires a competition for space. A mechanical crosstalk can arise from this competition. In this article, we dissect the biomechanical sequence caused by a controlled compressive stress on multicellular spheroids (MCSs) used as a tumor model system. On timescales of minutes, we show that a compressive stress causes a reduction of the MCS volume, linked to a reduction of the cell volume in the core of the MCS. On timescales of hours, we observe a reversible induction of the proliferation inhibitor, p27Kip1, from the center to the periphery of the spheroid. On timescales of days, we observe that cells are blocked in the cell cycle at the late G1 checkpoint, the restriction point. We show that the effect of pressure on the proliferation can be antagonized by silencing p27Kip1. Finally, we quantify a clear correlation between the pressure-induced volume change and the growth rate of the spheroid. The compression-induced proliferation arrest that we studied is conserved for five cell lines, and is completely reversible. It demonstrates a generic crosstalk between mechanical stresses and the key players of cell cycle regulation. Our results suggest a role of volume change in the sensitivity to pressure, and that p27Kip1 is strongly influenced by this change.

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Année de publication : 2013

Edouard Hannezo, Jacques Prost, Jean-Francois Joanny (2013 Dec 23)

Theory of epithelial sheet morphology in three dimensions.

Proceedings of the National Academy of Sciences of the United States of America : 27-32 : DOI : 10.1073/pnas.1312076111 En savoir plus
Résumé

Morphogenesis during embryo development requires the coordination of mechanical forces to generate the macroscopic shapes of organs. We propose a minimal theoretical model, based on cell adhesion and actomyosin contractility, which describes the various shapes of epithelial cells and the bending and buckling of epithelial sheets, as well as the relative stability of cellular tubes and spheres. We show that, to understand these processes, a full 3D description of the cells is needed, but that simple scaling laws can still be derived. The morphologies observed in vivo can be understood as stable points of mechanical equations and the transitions between them are either continuous or discontinuous. We then focus on epithelial sheet bending, a ubiquitous morphogenetic process. We calculate the curvature of an epithelium as a function of actin belt tension as well as of cell-cell and and cell-substrate tension. The model allows for a comparison of the relative stabilities of spherical or cylindrical cellular structures (acini or tubes). Finally, we propose a unique type of buckling instability of epithelia, driven by a flattening of individual cell shapes, and discuss experimental tests to verify our predictions.

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Pedro Campinho, Martin Behrndt, Jonas Ranft, Thomas Risler, Nicolas Minc, Carl-Philipp Heisenberg (2013 Nov 12)

Tension-oriented cell divisions limit anisotropic tissue tension in epithelial spreading during zebrafish epiboly.

Nature cell biology : 1405-14 : DOI : 10.1038/ncb2869 En savoir plus
Résumé

Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.

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Kaoru Sugimura, Yohanns Bellaïche, François Graner, Philippe Marcq, Shuji Ishihara (2013 Oct 11)

Robustness of force and stress inference in an epithelial tissue.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference : 2712-5 : DOI : 10.1109/EMBC.2013.6610100 En savoir plus
Résumé

During morphogenesis, the shape of a tissue emerges from collective cellular behaviors, which are in part regulated by mechanical and biochemical interactions between cells. Quantification of force and stress is therefore necessary to analyze the mechanisms controlling tissue morphogenesis. Recently, a mechanical measurement method based on force inference from cell shapes and connectivity has been developed. It is non-invasive, and can provide space-time maps of force and stress within an epithelial tissue, up to prefactors. We previously performed a comparative study of three force-inference methods, which differ in their approach of treating indefiniteness in an inverse problem between cell shapes and forces. In the present study, to further validate and compare the three force inference methods, we tested their robustness by measuring temporal fluctuation of estimated forces. Quantitative data of cell-level dynamics in a developing tissue suggests that variation of forces and stress will remain small within a short period of time (~minutes). Here, we showed that cell-junction tensions and global stress inferred by the Bayesian force inference method varied less with time than those inferred by the method that estimates only tension. In contrast, the amplitude of temporal fluctuations of estimated cell pressures differs less between different methods. Altogether, the present study strengthens the validity and robustness of the Bayesian force-inference method.

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Hervé Turlier, Basile Audoly, Jacques Prost, Jean-François Joanny (2013 Sep 10)

Furrow constriction in animal cell cytokinesis.

Biophysical journal : 114-23 : DOI : 10.1016/j.bpj.2013.11.014 En savoir plus
Résumé

Cytokinesis is the process of physical cleavage at the end of cell division; it proceeds by ingression of an acto-myosin furrow at the equator of the cell. Its failure leads to multinucleated cells and is a possible cause of tumorigenesis. Here, we calculate the full dynamics of furrow ingression and predict cytokinesis completion above a well-defined threshold of equatorial contractility. The cortical acto-myosin is identified as the main source of mechanical dissipation and active forces. Thereupon, we propose a viscous active nonlinear membrane theory of the cortex that explicitly includes actin turnover and where the active RhoA signal leads to an equatorial band of myosin overactivity. The resulting cortex deformation is calculated numerically, and reproduces well the features of cytokinesis such as cell shape and cortical flows toward the equator. Our theory gives a physical explanation of the independence of cytokinesis duration on cell size in embryos. It also predicts a critical role of turnover on the rate and success of furrow constriction. Scaling arguments allow for a simple interpretation of the numerical results and unveil the key mechanism that generates the threshold for cytokinesis completion: cytoplasmic incompressibility results in a competition between the furrow line tension and the cell poles’ surface tension.

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Année de publication : 2014

Olivier Cochet-Escartin, Jonas Ranft, Pascal Silberzan, Philippe Marcq (2013 Jul 20)

Border forces and friction control epithelial closure dynamics.

Biophysical journal : 65-73 : DOI : 10.1016/j.bpj.2013.11.015 En savoir plus
Résumé

We study the closure dynamics of a large number of well-controlled circular apertures within an epithelial monolayer, where the collective cell migration responsible for epithelization is triggered by the removal of a spatial constraint rather than by scratching. Based on experimental observations, we propose a physical model that takes into account border forces, friction with the substrate, and tissue rheology. Border protrusive activity drives epithelization despite the presence of a contractile actomyosin cable at the periphery of the wound. The closure dynamics is quantified by an epithelization coefficient, defined as the ratio of protrusive stress to tissue-substrate friction, that allows classification of different phenotypes. The same analysis demonstrates a distinct signature for human cells bearing the oncogenic RasV12 mutation, demonstrating the potential of the approach to quantitatively characterize metastatic transformations.

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Année de publication : 2013

Morgan Delarue, Fabien Montel, Ouriel Caen, Jens Elgeti, Jean-Michel Siaugue, Danijela Vignjevic, Jacques Prost, Jean-François Joanny, Giovanni Cappello (2013 Apr 16)

Mechanical control of cell flow in multicellular spheroids.

Physical review letters : 138103 En savoir plus
Résumé

Collective cell motion is observed in a wide range of biological processes. In tumors, physiological gradients of nutrients, growth factors, or even oxygen give rise to gradients of proliferation. We show using fluorescently labeled particles that these gradients drive a velocity field resulting in a cellular flow in multicellular spheroids. Under mechanical stress, the cellular flow is drastically reduced. We describe the results with a hydrodynamic model that considers only convection of the particles by the cellular flow.

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Année de publication : 2012

L Dinis, P Martin, J Barral, J Prost, J F Joanny (2012 Dec 11)

Fluctuation-response theorem for the active noisy oscillator of the hair-cell bundle.

Physical review letters : 160602 En savoir plus
Résumé

The hair bundle of sensory cells in the vertebrate ear provides an example of a noisy oscillator close to a Hopf bifurcation. The analysis of the data from both spontaneous and forced oscillations shows a strong violation of the fluctuation-dissipation theorem, revealing the presence of an underlying active process that keeps the system out of equilibrium. Nevertheless, we show that a generalized fluctuation-dissipation theorem, valid for nonequilibrium steady states, is fulfilled within the limits of our experimental accuracy and computational approximations, when the adequate conjugate degrees of freedom are chosen.

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Edouard Hannezo, Jacques Prost, Jean-François Joanny (2012 Oct 4)

Mechanical instabilities of biological tubes.

Physical review letters : 018101 En savoir plus
Résumé

We study theoretically the morphologies of biological tubes affected by various pathologies. When epithelial cells grow, the negative tension produced by their division provokes a buckling instability. Several shapes are investigated: varicose, dilated, sinuous, or sausagelike. They are all found in pathologies of tracheal, renal tubes, or arteries. The final shape depends crucially on the mechanical parameters of the tissues: Young’s 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.

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