Approches physiques de problématiques biologiques

Publications de l’équipe

Année de publication : 2016

Vincent Nier, Shreyansh Jain, Chwee Teck Lim, Shuji Ishihara, Benoit Ladoux, Philippe Marcq (2016 Apr 14)

Inference of Internal Stress in a Cell Monolayer.

Biophysical journal : 1625-35 : DOI : 10.1016/j.bpj.2016.03.002 En savoir plus
Résumé

We combine traction force data with Bayesian inversion to obtain an absolute estimate of the internal stress field of a cell monolayer. The method, Bayesian inversion stress microscopy, is validated using numerical simulations performed in a wide range of conditions. It is robust to changes in each ingredient of the underlying statistical model. Importantly, its accuracy does not depend on the rheology of the tissue. We apply Bayesian inversion stress microscopy to experimental traction force data measured in a narrow ring of cohesive epithelial cells, and check that the inferred stress field coincides with that obtained by direct spatial integration of the traction force data in this quasi one-dimensional geometry.

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Ken Sekimoto, Jacques Prost (2016 Mar 31)

Elastic Anisotropy Scenario for Cooperative Binding of Kinesin-Coated Beads on Microtubules.

The journal of physical chemistry. B En savoir plus
Résumé

Muto et al. reported in 2005 an observation called cooperative binding, according to which the initial binding of a bead covered with active kinesins on a microtubule filament was capable of favoring the subsequent binding of similar beads on the same filament up to distances of the order of a few microns. This positive bias is stronger ahead of the initially bound bead than behind. We explain this effect by combining the recently proposed notion of shear screening length with the notion of localized tubulin conformational transition induced by motor binding. Elastic terms linked to the polarity of protofilaments, up to now ignored, provide adequate description to the long-range elastic shear generated by motor binding. The subsequent binding is favored when and where the shear displacement of protofilaments meets the requirement for specific strong binding. We propose experimental tests of our model, which open the way to a new type of spectroscopy for biomolecular processes.

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Edouard Hannezo, Alice Coucke, Jean-François Joanny (2016 Mar 18)

Interplay of migratory and division forces as a generic mechanism for stem cell patterns.

Physical review. E : 022405 En savoir plus
Résumé

In many adult tissues, stem cells and differentiated cells are not homogeneously distributed: stem cells are arranged in periodic « niches, » and differentiated cells are constantly produced and migrate out of these niches. In this article, we provide a general theoretical framework to study mixtures of dividing and actively migrating particles, which we apply to biological tissues. We show in particular that the interplay between the stresses arising from active cell migration and stem cell division give rise to robust stem cell patterns. The instability of the tissue leads to spatial patterns which are either steady or oscillating in time. The wavelength of the instability has an order of magnitude consistent with the biological observations. We also discuss the implications of these results for future in vitro and in vivo experiments.

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Pierre Recho, Jonas Ranft, Philippe Marcq (2016 Jan 23)

One-dimensional collective migration of a proliferating cell monolayer.

Soft matter : 2381-91 : DOI : 10.1039/c5sm02857d En savoir plus
Résumé

The importance of collective cellular migration during embryogenesis and tissue repair asks for a sound understanding of underlying principles and mechanisms. Here, we address recent in vitro experiments on cell monolayers, which show that the advancement of the leading edge relies on cell proliferation and protrusive activity at the tissue margin. Within a simple viscoelastic mechanical model amenable to detailed analysis, we identify a key parameter responsible for tissue expansion, and we determine the dependence of the monolayer velocity as a function of measurable rheological parameters. Our results allow us to discuss the effects of pharmacological perturbations on the observed tissue dynamics.

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Thomas Risler, Aurélien Peilloux, Jacques Prost (2016 Jan 2)

Homeostatic Fluctuations of a Tissue Surface.

Physical review letters : 258104 : DOI : 10.1103/PhysRevLett.115.258104 En savoir plus
Résumé

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.

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Année de publication : 2015

Quentin Vagne, Matthew S Turner, Pierre Sens (2015 Dec 15)

Sensing Size through Clustering in Non-Equilibrium Membranes and the Control of Membrane-Bound Enzymatic Reactions.

PloS one : e0143470 : DOI : 10.1371/journal.pone.0143470 En savoir plus
Résumé

The formation of dynamical clusters of proteins is ubiquitous in cellular membranes and is in part regulated by the recycling of membrane components. We show, using stochastic simulations and analytic modeling, that the out-of-equilibrium cluster size distribution of membrane components undergoing continuous recycling is strongly influenced by lateral confinement. This result has significant implications for the clustering of plasma membrane proteins whose mobility is hindered by cytoskeletal « corrals » and for protein clustering in cellular organelles of limited size that generically support material fluxes. We show how the confinement size can be sensed through its effect on the size distribution of clusters of membrane heterogeneities and propose that this could be regulated to control the efficiency of membrane-bound reactions. To illustrate this, we study a chain of enzymatic reactions sensitive to membrane protein clustering. The reaction efficiency is found to be a non-monotonic function of the system size, and can be optimal for sizes comparable to those of cellular organelles.

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Sophie Marbach, Amélie Luise Godeau, Daniel Riveline, Jean-François Joanny, Jacques Prost (2015 Nov 22)

Theoretical study of actin layers attachment and separation.

The European physical journal. E, Soft matter : 122 : DOI : 10.1140/epje/i2015-15122-4 En savoir plus
Résumé

We use the theory of active gels to study theoretically the merging and separation of two actin dense layers akin to cortical layers of animal cells. The layers bind at a distance equal to twice the thickness of a free layer, thus forming a single dense layer, similar in this sense to a lamellipodium. When that unique layer is stretched apart, it is resilient to break apart up to a critical length larger than twice the thickness of a free layer. We show that this behavior can result from the high contractile properties of the actomyosin gel due to the activity of myosin molecular motors. Furthermore, we establish that the stability of the stretched single layer is highly dependent on the properties of the gel. Indeed, the nematic order of the actin filaments along the polymerizing membranes is a destabilizing factor.

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Sham Tlili, Cyprien Gay, François Graner, Philippe Marcq, François Molino, Pierre Saramito (2015 Nov 6)

Erratum to: Colloquium: Mechanical formalisms for tissue dynamics.

The European physical journal. E, Soft matter : 115 : DOI : 10.1140/epje/i2015-15115-3 En savoir plus
Résumé

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Grégory Beaune, Françoise M Winnik, Françoise Brochard-Wyart (2015 Oct 29)

Formation of Tethers from Spreading Cellular Aggregates.

Langmuir : the ACS journal of surfaces and colloids : 12984-92 : DOI : 10.1021/acs.langmuir.5b02785 En savoir plus
Résumé

Membrane tubes are commonly extruded from cells and vesicles when a point-like force is applied on the membrane. We report here the unexpected formation of membrane tubes from lymph node cancer prostate (LNCaP) cell aggregates in the absence of external applied forces. The spreading of LNCaP aggregates deposited on adhesive glass substrates coated with fibronectin is very limited because cell-cell adhesion is stronger than cell-substrate adhesion. Some cells on the aggregate periphery are very motile and try to escape from the aggregate, leading to the formation of membrane tubes. Tethered networks and exchange of cargos between cells were observed as well. Growth of the tubes is followed by either tube retraction or tube rupture. Hence, even very cohesive cells are successful in escaping aggregates, which may lead to epithelial mesenchymal transition and tumor metastasis. We interpret the dynamics of formation and retraction of tubes in the framework of membrane mechanics.

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A Y Grosberg, J-F Joanny (2015 Oct 15)

Nonequilibrium statistical mechanics of mixtures of particles in contact with different thermostats.

Physical review. E, Statistical, nonlinear, and soft matter physics : 032118 : DOI : 10.1103/PhysRevE.92.032118 En savoir plus
Résumé

We introduce a novel type of locally driven systems made of two types of particles (or a polymer with two types of monomers) subject to a chaotic drive with approximately white noise spectrum, but different intensity; in other words, particles of different types are in contact with thermostats at different temperatures. We present complete systematic statistical mechanics treatment starting from first principles. Although we consider only corrections to the dilute limit due to pairwise collisions between particles, meaning we study a nonequilibrium analog of the second virial approximation, we find that the system exhibits a surprisingly rich behavior. In particular, pair correlation function of particles has an unusual quasi-Boltzmann structure governed by an effective temperature distinct from that of any of the two thermostats. We also show that at sufficiently strong drive the uniformly mixed system becomes unstable with respect to steady states consisting of phases enriched with different types of particles. In the second virial approximation, we define nonequilibrium « chemical potentials » whose gradients govern diffusion fluxes and a nonequilibrium « osmotic pressure, » which governs the mechanical stability of the interface.

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Vincent Nier, Maxime Deforet, Guillaume Duclos, Hannah G Yevick, Olivier Cochet-Escartin, Philippe Marcq, Pascal Silberzan (2015 Jul 21)

Tissue fusion over nonadhering surfaces.

Proceedings of the National Academy of Sciences of the United States of America : 9546-51 : DOI : 10.1073/pnas.1501278112 En savoir plus
Résumé

Tissue fusion eliminates physical voids in a tissue to form a continuous structure and is central to many processes in development and repair. Fusion events in vivo, particularly in embryonic development, often involve the purse-string contraction of a pluricellular actomyosin cable at the free edge. However, in vitro, adhesion of the cells to their substrate favors a closure mechanism mediated by lamellipodial protrusions, which has prevented a systematic study of the purse-string mechanism. Here, we show that monolayers can cover well-controlled mesoscopic nonadherent areas much larger than a cell size by purse-string closure and that active epithelial fluctuations are required for this process. We have formulated a simple stochastic model that includes purse-string contractility, tissue fluctuations, and effective friction to qualitatively and quantitatively account for the dynamics of closure. Our data suggest that, in vivo, tissue fusion adapts to the local environment by coordinating lamellipodial protrusions and purse-string contractions.

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Edouard Hannezo, Bo Dong, Pierre Recho, Jean-François Joanny, Shigeo Hayashi (2015 Jun 17)

Cortical instability drives periodic supracellular actin pattern formation in epithelial tubes.

Proceedings of the National Academy of Sciences of the United States of America : 8620-5 : DOI : 10.1073/pnas.1504762112 En savoir plus
Résumé

An essential question of morphogenesis is how patterns arise without preexisting positional information, as inspired by Turing. In the past few years, cytoskeletal flows in the cell cortex have been identified as a key mechanism of molecular patterning at the subcellular level. Theoretical and in vitro studies have suggested that biological polymers such as actomyosin gels have the property to self-organize, but the applicability of this concept in an in vivo setting remains unclear. Here, we report that the regular spacing pattern of supracellular actin rings in the Drosophila tracheal tubule is governed by a self-organizing principle. We propose a simple biophysical model where pattern formation arises from the interplay of myosin contractility and actin turnover. We validate the hypotheses of the model using photobleaching experiments and report that the formation of actin rings is contractility dependent. Moreover, genetic and pharmacological perturbations of the physical properties of the actomyosin gel modify the spacing of the pattern, as the model predicted. In addition, our model posited a role of cortical friction in stabilizing the spacing pattern of actin rings. Consistently, genetic depletion of apical extracellular matrix caused strikingly dynamic movements of actin rings, mirroring our model prediction of a transition from steady to chaotic actin patterns at low cortical friction. Our results therefore demonstrate quantitatively that a hydrodynamical instability of the actin cortex can trigger regular pattern formation and drive morphogenesis in an in vivo setting.

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Pierre Sens, Julie Plastino (2015 Jun 11)

Membrane tension and cytoskeleton organization in cell motility.

Journal of physics. Condensed matter : an Institute of Physics journal : 273103 : DOI : 10.1088/0953-8984/27/27/273103 En savoir plus
Résumé

Cell membrane shape changes are important for many aspects of normal biological function, such as tissue development, wound healing and cell division and motility. Various disease states are associated with deregulation of how cells move and change shape, including notably tumor initiation and cancer cell metastasis. Cell motility is powered, in large part, by the controlled assembly and disassembly of the actin cytoskeleton. Much of this dynamic happens in close proximity to the plasma membrane due to the fact that actin assembly factors are membrane-bound, and thus actin filaments are generally oriented such that their growth occurs against or near the membrane. For a long time, the membrane was viewed as a relatively passive scaffold for signaling. However, results from the last five years show that this is not the whole picture, and that the dynamics of the actin cytoskeleton are intimately linked to the mechanics of the cell membrane. In this review, we summarize recent findings concerning the role of plasma membrane mechanics in cell cytoskeleton dynamics and architecture, showing that the cell membrane is not just an envelope or a barrier for actin assembly, but is a master regulator controlling cytoskeleton dynamics and cell polarity.

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Sham Tlili, Cyprien Gay, François Graner, Philippe Marcq, François Molino, Pierre Saramito (2015 May 10)

Colloquium: Mechanical formalisms for tissue dynamics.

The European physical journal. E, Soft matter : 121 : DOI : 10.1140/epje/i2015-15033-4 En savoir plus
Résumé

The understanding of morphogenesis in living organisms has been renewed by tremendous progress in experimental techniques that provide access to cell scale, quantitative information both on the shapes of cells within tissues and on the genes being expressed. This information suggests that our understanding of the respective contributions of gene expression and mechanics, and of their crucial entanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assist the design and interpretation of experiments, point out the main ingredients and assumptions, and ultimately lead to predictions. The newly accessible local information thus calls for a reflection on how to select suitable classes of mechanical models. We review both mechanical ingredients suggested by the current knowledge of tissue behaviour, and modelling methods that can help generate a rheological diagram or a constitutive equation. We distinguish cell scale (« intra-cell ») and tissue scale (« inter-cell ») contributions. We recall the mathematical framework developed for continuum materials and explain how to transform a constitutive equation into a set of partial differential equations amenable to numerical resolution. We show that when plastic behaviour is relevant, the dissipation function formalism appears appropriate to generate constitutive equations; its variational nature facilitates numerical implementation, and we discuss adaptations needed in the case of large deformations. The present article gathers theoretical methods that can readily enhance the significance of the data to be extracted from recent or future high throughput biomechanical experiments.

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Ricard Alert, Jaume Casademunt, Jan Brugués, Pierre Sens (2015 Apr 23)

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

Biophysical journal : 1878-86 : DOI : 10.1016/j.bpj.2015.02.027 En savoir plus
Résumé

We propose a model for membrane-cortex adhesion that 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.

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