Approches physiques de problématiques biologiques

Publications de l’équipe

Année de publication : 2011

Fabien Montel, Morgan Delarue, Jens Elgeti, Laurent Malaquin, Markus Basan, Thomas Risler, Bernard Cabane, Danijela Vignjevic, Jacques Prost, Giovanni Cappello, Jean-François Joanny (2011 Mar 3)

Stress clamp experiments on multicellular tumor spheroids.

Physical review letters : 188102 En savoir plus
Résumé

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.

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N Yoshinaga, J-F Joanny, J Prost, P Marcq (2011 Jan 15)

Polarity patterns of stress fibers.

Physical review letters : 238103 En savoir plus
Résumé

Stress fibers are contractile actomyosin bundles commonly observed in the cytoskeleton of metazoan cells. The spatial profile of the polarity of actin filaments inside contractile actomyosin bundles is either monotonic (graded) or periodic (alternating). In the framework of linear irreversible thermodynamics, we write the constitutive equations for a polar, active, elastic one-dimensional medium. An analysis of the resulting equations for the dynamics of polarity shows that the transition from graded to alternating polarity patterns is a nonequilibrium Lifshitz point. Active contractility is a necessary condition for the emergence of sarcomeric, alternating polarity patterns.

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Année de publication : 2010

Sandrine Morlot, Martin Lenz, Jacques Prost, Jean-François Joanny, Aurélien Roux (2010 Nov 30)

Deformation of dynamin helices damped by membrane friction.

Biophysical journal : 3580-8 : DOI : 10.1016/j.bpj.2010.10.015 En savoir plus
Résumé

Dynamin and other proteins of the dynamin superfamily are widely used by cells to sever lipid bilayers. During this process, a short helical dynamin polymer (one to three helical turns) assembles around a membrane tubule and reduces its radius and pitch upon guanosine triphosphate hydrolysis. This deformation is thought to be crucial for dynamin’s severing action and results in an observable twisting of the helix. Here, we quantitatively characterize the dynamics of this deformation by studying long dynamin helices (many helical turns). We perform in vitro experiments where we attach small beads to the dynamin helix and track their rotation in real time, thus collecting information about the space and time dependence of the deformation. We develop a theoretical formalism to predict the dynamics of a mechanically continuous helix deforming on long timescales. Longer helices deform more slowly, as predicted by theory. This could account for the previously reported observation that they are less fission-competent. Comparison between experiments and our model indicates that the deformation dynamics is dominated by the draining of the membrane out of the helix, allowing quantification of helix-membrane interactions.

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Jonas Ranft, Markus Basan, Jens Elgeti, Jean-François Joanny, Jacques Prost, Frank Jülicher (2010 Nov 17)

Fluidization of tissues by cell division and apoptosis.

Proceedings of the National Academy of Sciences of the United States of America : 20863-8 : DOI : 10.1073/pnas.1011086107 En savoir plus
Résumé

During the formation of tissues, cells organize collectively by cell division and apoptosis. The multicellular dynamics of such systems is influenced by mechanical conditions and can give rise to cell rearrangements and movements. We develop a continuum description of tissue dynamics, which describes the stress distribution and the cell flow field on large scales. In the absence of division and apoptosis, we consider the tissue to behave as an elastic solid. Cell division and apoptosis introduce stress sources that, in general, are anisotropic. By combining cell number balance with dynamic equations for the stress source, we show that the tissue effectively behaves as a viscoelastic fluid with a relaxation time set by the rates of division and apoptosis. If the system is confined in a fixed volume, it reaches a homeostatic state in which division and apoptosis balance. In this state, cells undergo a diffusive random motion driven by the stochasticity of division and apoptosis. We calculate the expression for the effective diffusion coefficient as a function of the tissue parameters and compare our results concerning both diffusion and viscosity to simulations of multicellular systems using dissipative particle dynamics.

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Martin Lenz, Jacques Prost, Jean-François Joanny (2010 Oct 21)

Actin cross-linkers and the shape of stereocilia.

Biophysical journal : 2423-33 : DOI : 10.1016/j.bpj.2010.07.065 En savoir plus
Résumé

Stereocilia are actin-based cellular protrusions essential for hearing. We propose that they are shaped by the detachment dynamics of actin cross-linkers, in particular espin. We account for experimentally observed stereocilium shapes, treadmilling velocity to length relationship, espin 1 localization profile, and microvillus length to espin level relationship. If the cross-linkers are allowed to reattach, our model yields a dynamical phase transition toward unbounded growth. Considering the simplified case of a noninteracting, one-filament system, we calculate the length probability distribution in the growing phase and its stationary form in a continuum approximation of the finite-length phase. Numerical simulations of interacting filaments suggest an anomalous power-law divergence of the protrusion length at the growth transition, which could be a universal feature of cross-linked depolymerizing systems.

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T Guérin, J Prost, J-F Joanny (2010 Sep 28)

Dynamic instabilities in assemblies of molecular motors with finite stiffness.

Physical review letters : 248102 En savoir plus
Résumé

We propose a two-state « soft-motor » model for the collective behavior of molecular motors which takes into account both the internal motor stiffness and the periodic interaction with the filament. As in the Prandtl-Tomlinson model of tribology, the important parameter of the model is the pinning parameter, which compares the stiffness of the motors to the stiffness of the potential. The model predicts dynamic instabilities in two disconnected regions of parameter space. These parameter ranges correspond to two existing theories of motor assemblies, the rigid two-state model and the crossbridge model. The model also predicts a discontinuity of the slope of the force-velocity relation at small velocities.

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Jean-François Joanny, Sriram Ramaswamy (2010 Sep 3)

Biological physics: Filaments band together.

Nature : 33-4 : DOI : 10.1038/467033a En savoir plus
Résumé

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Cécile Leduc, Otger Campàs, Jean-François Joanny, Jacques Prost, Patricia Bassereau (2010 Jul 1)

Mechanism of membrane nanotube formation by molecular motors.

Biochimica et biophysica acta : 1798 : 1418-1426 : DOI : 10.1016/j.bbamem.2009.11.012 En savoir plus
Résumé

Membrane nanotubes are ubiquitous in eukaryotic cells due to Their involvement in the communication entre Many different compartments membrane. They are very dynamical structures, qui Generally are extended along the microtubule network. One feasible mechanism of tube formation Involves the share of molecular motors, can generate qui The Necessary strength to pull the tubes along the cytoskeleton tracks. HOWEVER, It has not so far-been feasible to image in living organisms Simultaneously Both tube formation and the molecular motors Involved in the process. The Reasons for this are technological Mainly. To Overcome thesis limitations and to elucidate in detail the mechanism of tube formation, Many experiments-have beens Developed over the last years in cell-free environments. In the present review, we present the results, qui-have-been therefor obtained in vitro in cell extracts Either or with purified and artificial components. In Particular, we will focus on a biomimetic system, qui Involves Unilamellar Giant Vesicles, kinesin-1 motors and microtubules in the presence of ATP. We present Both theoretical and experimental results based on fluorescence microscopy That elucidate the dynamics of membrane tube formation, growth and stalling.

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Markus Basan, Timon Idema, Martin Lenz, Jean-François Joanny, Thomas Risler (2010 Jun 17)

A reaction-diffusion model of the cadherin-catenin system: a possible mechanism for contact inhibition and implications for tumorigenesis.

Biophysical journal : 2770-9 : DOI : 10.1016/j.bpj.2010.03.051 En savoir plus
Résumé

Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors. When two cells touch, an adhesion link is created between them by means of transmembrane E-cadherin proteins. Simultaneously, their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links. Here, we propose a detailed quantitative model of the role of cytoplasmic beta-catenin and alpha-catenin proteins in this process, treated as a reaction-diffusion system. Upon cell-cell contact the concentration in alpha-catenin dimers increases, inhibiting actin branching and thereby reducing cellular motility and expansion pressure. This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin, beta-catenin, and alpha-catenin in the cellular phenotype and in tumorigenesis. In particular, we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene. Potential direct tests of our model are discussed.

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Padinhateeri Ranjith, Kirone Mallick, Jean-François Joanny, David Lacoste (2010 Apr 23)

Role of ATP-hydrolysis in the dynamics of a single actin filament.

Biophysical journal : 1418-27 : DOI : 10.1016/j.bpj.2009.12.4306 En savoir plus
Résumé

We study the stochastic dynamics of growth and shrinkage of single actin filaments taking into account insertion, removal, and ATP hydrolysis of subunits either according to the vectorial mechanism or to the random mechanism. In a previous work, we developed a model for a single actin or microtubule filament where hydrolysis occurred according to the vectorial mechanism: the filament could grow only from one end, and was in contact with a reservoir of monomers. Here we extend this approach in two ways–by including the dynamics of both ends and by comparing two possible mechanisms of ATP hydrolysis. Our emphasis is mainly on two possible limiting models for the mechanism of hydrolysis within a single filament, namely the vectorial or the random model. We propose a set of experiments to test the nature of the precise mechanism of hydrolysis within actin filaments.

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I Erukhimovich, A Johner, J F Joanny (2010 Feb 23)

Depletion of ideal polymer chains near a spherical colloid particle beyond the Dirichlet boundary conditions.

The European physical journal. E, Soft matter : 115-24 : DOI : 10.1140/epje/i2010-10568-4 En savoir plus
Résumé

We reconsider the depletion interaction of an ideal polymer chain, characterized by the gyration radius R(G) and bond length a , and an impenetrable spherical colloid particle of radius R . Forbidding the polymer-colloid penetration explicitly (by the use of Mayer functions) without any other requirement we derive and solve analytically an integral equation for the chain partition function of a long ideal polymer chain for the spherical geometry. We find that the correction to the solution of the Dirichlet problem depends on the ratios R/R (G) and R/a . The correction vanishes for the continuous chain model (i.e. in the limit R/R (G) –> 0 and R/a –> infinity but stays finite (even for an infinite chain) for the discrete chain model. The correction can become substantial in the case of nano-colloids (the so-called protein limit).

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Markus Basan, Thomas Risler, Jean-François Joanny, Xavier Sastre-Garau, Jacques Prost (2010 Feb 2)

Homeostatic competition drives tumor growth and metastasis nucleation.

HFSP journal : 265-72 : DOI : 10.2976/1.3086732 En savoir plus
Résumé

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.

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Thomas Guérin, Jacques Prost, Pascal Martin, Jean-François Joanny (2010 Jan 16)

Coordination and collective properties of molecular motors: theory.

Current opinion in cell biology : 14-20 : DOI : 10.1016/j.ceb.2009.12.012 En savoir plus
Résumé

Many cellular processes require molecular motors to produce motion and forces. Single molecule experiments have led to a precise description of how a motor works. Under most physiological conditions, however, molecular motors operate in groups. Interactions between motors yield collective behaviors that cannot be explained only from single molecule properties. The aim of this paper is to review the various theoretical descriptions that explain the emergence of collective effects in molecular motor assemblies. These include bidirectional motion, hysteretic behavior, spontaneous oscillations, and self-organization into dynamical structures. We discuss motors acting on the cytoskeleton both in a prescribed geometry such as in muscles or flagella and in the cytoplasm.

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Année de publication : 2009

Jean-Yves Tinevez, Ulrike Schulze, Guillaume Salbreux, Julia Roensch, Jean-François Joanny, Ewa Paluch (2009 Oct 23)

Role of cortical tension in bleb growth.

Proceedings of the National Academy of Sciences of the United States of America : 18581-6 : DOI : 10.1073/pnas.0903353106 En savoir plus
Résumé

Blebs are spherical membrane protrusions often observed during cell migration, cell spreading, cytokinesis, and apoptosis, both in cultured cells and in vivo. Bleb expansion is thought to be driven by the contractile actomyosin cortex, which generates hydrostatic pressure in the cytoplasm and can thus drive herniations of the plasma membrane. However, the role of cortical tension in bleb formation has not been directly tested, and despite the importance of blebbing, little is known about the mechanisms of bleb growth. In order to explore the link between cortical tension and bleb expansion, we induced bleb formation on cells with different tensions. Blebs were nucleated in a controlled manner by laser ablation of the cortex, mimicking endogenous bleb nucleation. Cortical tension was modified by treatments affecting the level of myosin activity or proteins regulating actin turnover. We show that there is a critical tension below which blebs cannot expand. Above this threshold, the maximal size of a bleb strongly depends on tension, and this dependence can be fitted with a model of the cortex as an active elastic material. Together, our observations and model allow us to relate bleb shape parameters to the underlying cellular mechanics and provide insights as to how bleb formation can be biochemically regulated during cell motility.

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G Salbreux, J Prost, J F Joanny (2009 Oct 2)

Hydrodynamics of cellular cortical flows and the formation of contractile rings.

Physical review letters : 058102 En savoir plus
Résumé

We propose a mechanism for the formation of contractile rings and the apparition of a flow in the cortical layer of cells undergoing cytokinesis at the end of cell division or during the healing of a wound in the cortex of Xenopus eggs. We generalize the hydrodynamic active gel theory along the lines of thin shell theory of continuum elasticity to describe the cell cortex. As in liquid crystal physics, the flow couples to the orientation of the actin filaments. The cortical flow is driven by an increased density of myosin motors in the cortex, and orients the filaments to form the ring.

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