Physique multi-échelle de la morphogénèse / Multiscale physics of morphogenesis

Recherche Page web : https://www.college-de-france.fr/site/en-cirb/Turlier.htm. Introduction Invaluable progress has been made last decades in the molecular, genetic and cellular characterization of morphogenetic processes. Yet, the precise physical processes governing the shape and dynamics of cells remain poorly characterized. The laboratory is developing theoretical models of morphogenesis, combining physics, mechanics and advanced numerical simulations. To understand how morphology contro..

A viscous active shell theory of the cell cortex

The cell cortex is a thin layer beneath the plasma membrane that gives animal cells mechanical resistance and drives most of their shape changes, from migration, division to multicellular morphogenesis. It is mainly composed of actin filaments, actin binding proteins, and myosin molecular motors. Constantly stirred by myosin motors and under fast renewal, this material may be well described by viscous and contractile active-gel theories. Here, we assume that the cortex is a thin viscous shell with non-negligible curvature and use asymptotic expansions to find the leading-order equations describing its shape dynamics, starting from constitutive equations for an incompressible viscous active gel. Reducing the three-dimensional equations leads to a Koiter-like shell theory, where both resistance to stretching and bending rates are present. Constitutive equations are completed by a kinematical equation describing the evolution of the cortex thickness with turnover. We show that tension and moment resultants depend not only on the shell deformation rate and motor activity but also on the active turnover of the material, which may also exert either contractile or extensile stress. Using the finite-element method, we implement our theory numerically to study two biological examples of drastic cell shape changes: osmotic shocks and cell division. Our work provides a numerical implementation of thin active viscous layers and a generic theoretical framework to develop shell theories for slender active biological structures.Comment: 37 pages, 13 figures, 1 appendi

Façonner la cellule : théories de membranes actives

The surface of animal cells is a thin layer composed of a lipid bilayer and a cytoskeleton. Cells control their shape dynamically by remodeling their cytoskeleton via active processes. In a first part, we consider the actomyosin cortex and its role in cytokinesis, the last stage of cell division. We formulate a viscous-active membrane mechanical theory of the cortical layer. The Lagrangian formulation of the theory is implemented numerically to study large cortical deformations during cytokinesis. We show that an equatorial band of myosin overactivity is sufficient to reproduce the formation and ingression of a cleavage furrow. We predict cytokinesis above a well-defined threshold of equatorial contractility and propose a physical explanation of the independence of cytokinesis duration on cell size in embryos. Scaling arguments are proposed as a simple interpretation of the numerical results and unveil a key mechanism: cytoplasmic incompressibility results in a competition between the furrow line tension and the cell poles surface tension. In the second part, we study the red-blood cell membrane and propose a model for its active fluctuations. We consider both the thermal fluctuations of the lipid bilayer and the chemical fluctuations of the spectrin skeleton anchoring to the lipid bilayer. The constant supply of ATP, by weakening this anchoring, is proposed to give rise to extra-fluctuations of the membrane. These non-equilibrium fluctuations violate the fluctuation-dissipation theorem, in agreement with experimental measurements, thereby exhibiting the living nature of the red-blood cell.La surface des cellules animales est composée d'une bicouche lipidique et d'un cytosquelette. Les cellules contrôlent leur forme en remodelant leur cytosquelette par des processus actifs. Nous considérons tout d'abord le cortex d'actomyosine et son rôle lors la cytocinèse, dernière étape de la division cellulaire. Nous formulons une théorie mécanique de membrane de la couche corticale active et visqueuse. La formulation Lagrangienne de la théorie est implémentée numériquement pour étudier la cytocinèse en régime de larges déformations. Nous montrons qu'une bande d'hyperactivité de la myosine à l'équateur de la cellule suffit à reproduire la formation et la contraction du sillon de division. Nous prédisons le succès de la cytocinèse au delà d'un certain seuil de contractilité équatoriale et proposons une explication physique de l'indépendance de la durée de contraction avec la taille d'un embryon. Des arguments d'échelle permettent d'interpréter les résultats numériques et révèlent un mécanisme clé: l'incompressibilité du cytoplasme induit une compétition entre la tension de ligne du sillon et la tension de surface aux pôles. Nous étudions ensuite la membrane du globule rouge et proposons un modèle pour ses fluctuations actives. Nous considérons à la fois les fluctuations thermiques de la membrane et les fluctuations chimiques de l'ancrage des filaments de spectrine dans la membrane. Un apport constant d'ATP, en affaiblissant cet ancrage, est la source de fluctuations supplémentaires dans la membrane. Ces fluctuations hors-équilibre violent le théorème de fluctuation- dissipation, en accord avec les résultats expérimentaux, signe que les globules rouges sont vivants

Mechanics of tissue compaction

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Forme cellulaire (théories de membranes actives)

The surface of animal cells is a thin layer composed of a lipid bilayer and a cytoskeleton. Cells control their shape dynamically by remodeling their cytoskeleton via active processes. In a first part, we consider the actomyosin cortex and its role in cytokinesis, the last stage of cell division. We formulate a viscous-active membrane mechanical theory of the cortical layer. The Lagrangian formulation of the theory is implemented numerically to study large cortical deformations during cytokinesis. We show that an equatorial band of myosin overactivity is sufficient to reproduce the formation and ingression of a cleavage furrow. We predict cytokinesis above a well-defined threshold of equatorial contractility and propose a physical explanation of the independence of cytokinesis duration on cell size in embryos. Scaling arguments are proposed as a simple interpretation of the numerical results and unveil a key mechanism: cytoplasmic incompressibility results in a competition between the furrow line tension and the cell poles surface tension. In the second part, we study the red-blood cell membrane and propose a model for its active fluctuations. We consider both the thermal fluctuations of the lipid bilayer and the chemical fluctuations of the spectrin skeleton anchoring to the lipid bilayer. The constant supply of ATP, by weakening this anchoring, is proposed to give rise to extra-fluctuations of the membrane. These non-equilibrium fluctuations violate the fluctuation-dissipation theorem, in agreement with experimental measurements, thereby exhibiting the living nature of the red-blood cell.La surface des cellules animales est composée d'une bicouche lipidique et d'un cytosquelette. Les cellules contrôlent leur forme en remodelant leur cytosquelette par des processus actifs. Nous considérons tout d'abord le cortex d'actomyosine et son rôle lors la cytocinèse, dernière étape de la division cellulaire. Nous formulons une théorie mécanique de membrane de la couche corticale active et visqueuse. La formulation Lagrangienne de la théorie est implémentée numériquement pour étudier la cytocinèse en régime de larges déformations. Nous montrons qu'une bande d'hyperactivité de la myosine à l'équateur de la cellule suffit à reproduire la formation et la contraction du sillon de division. Nous prédisons le succès de la cytocinèse au delà d'un certain seuil de contractilité équatoriale et proposons une explication physique de l'indépendance de la durée de contraction avec la taille d'un embryon. Des arguments d'échelle permettent d'interpréter les résultats numériques et révèlent un mécanisme clé: l'incompressibilité du cytoplasme induit une compétition entre la tension de ligne du sillon et la tension de surface aux pôles. Nous étudions ensuite la membrane du globule rouge et proposons un modèle pour ses fluctuations actives. Nous considérons à la fois les fluctuations thermiques de la membrane et les fluctuations chimiques de l'ancrage des filaments de spectrine dans la membrane. Un apport constant d'ATP, en affaiblissant cet ancrage, est la source de fluctuations supplémentaires dans la membrane. Ces fluctuations hors-équilibre violent le théorème de fluctuation-dissipation, en accord avec les résultats expérimentaux, signe que les globules rouges sont vivants.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

A hydro-osmotic coarsening theory of biological cavity formation

International audienceFluid-filled biological cavities are ubiquitous, but their collective dynamics has remained largely unexplored from a physical perspective. Based on experimental observations in early embryos, we propose a model where a cavity forms through the coarsening of myriad of pressurized micrometric lumens, that interact by ion and fluid exchanges through the intercellular space. Performing extensive numerical simulations, we find that hydraulic fluxes lead to a self-similar coarsening of lumens in time, characterized by a robust dynamic scaling exponent. The collective dynamics is primarily controlled by hydraulic fluxes, which stem from lumen pressures differences and are dampened by water permeation through the membrane. Passive osmotic heterogeneities play, on the contrary, a minor role on cavity formation but active ion pumping can largely modify the coarsening dynamics: it prevents the lumen network from a collective collapse and gives rise to a novel coalescence-dominated regime exhibiting a distinct scaling law. Interestingly, we prove numerically that spatially biasing ion pumping may be sufficient to position the cavity, suggesting a novel mode of symmetry breaking to control tissue patterning. Providing generic testable predictions, our model forms a comprehensive theoretical basis for hydro-osmotic interaction between biological cavities, that shall find wide applications in embryo and tissue morphogenesis

Pulsatile cell-autonomous contractility drives compaction in the mouse embryo

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Asymmetric division of contractile domains couples cell positioning and fate specification.

During pre-implantation development, the mammalian embryo self-organizes into the blastocyst, which consists of an epithelial layer encapsulating the inner-cell mass (ICM) giving rise to all embryonic tissues. In mice, oriented cell division, apicobasal polarity and actomyosin contractility are thought to contribute to the formation of the ICM. However, how these processes work together remains unclear. Here we show that asymmetric segregation of the apical domain generates blastomeres with different contractilities, which triggers their sorting into inner and outer positions. Three-dimensional physical modelling of embryo morphogenesis reveals that cells internalize only when differences in surface contractility exceed a predictable threshold. We validate this prediction using biophysical measurements, and successfully redirect cell sorting within the developing blastocyst using maternal myosin (Myh9)-knockout chimaeric embryos. Finally, we find that loss of contractility causes blastomeres to show ICM-like markers, regardless of their position. In particular, contractility controls Yap subcellular localization, raising the possibility that mechanosensing occurs during blastocyst lineage specification. We conclude that contractility couples the positioning and fate specification of blastomeres. We propose that this ensures the robust self-organization of blastomeres into the blastocyst, which confers remarkable regulative capacities to mammalian embryos

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

International audienceCell 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