UMR168 – Laboratoire Physico-Chimie Curie

Publications de l’UMR 168

Année de publication : 2014

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.

Replier
Lin Jia, Di Cui, Jérôme Bignon, Aurelie Di Cicco, Joanna Wdzieczak-Bakala, Jianmiao Liu, Min-Hui Li (2014 May 19)

Reduction-responsive cholesterol-based block copolymer vesicles for drug delivery.

Biomacromolecules : 2206-17 : DOI : 10.1021/bm5003569 En savoir plus
Résumé

We developed a new robust reduction-responsive polymersome based on the amphiphilic block copolymer PEG-SS-PAChol. The stability and robustness were achieved by the smectic physical cross-linking of cholesterol-containing liquid crystal polymer PAChol in the hydrophobic layer. The reduction-sensitivity was introduced by the disulfide bridge (-S-S-) that links the hydrophilic PEG block and the hydrophobic PAChol block. We used a versatile synthetic strategy based on atom transfer radical polymerization (ATRP) to synthesize the reduction-responsive amphiphilic block copolymers. The reductive cleavage of the disulfide bridge in the block copolymers was first evidenced in organic solution. The partial destruction of PEG-SS-PAChol polymersomes in the presence of a reducing agent was then demonstrated by cryo-electron microscopy. Finally, the calcein release from PEG-SS-PAChol polymersomes triggered by glutathione (GSH) was observed both in PBS suspension and in vitro inside the macrophage cells. High GSH concentrations (≥35 mM in PBS or artificially enhanced in macrophage cells by GSH-OEt pretreatment) and long incubation time (in the order of hours) were, however, necessary to get significant calcein release. These polymersomes could be used as drug carriers with very long circulation profiles and slow release kinetics.

Replier
Laura Picas, Julien Viaud, Kristine Schauer, Stefano Vanni, Karim Hnia, Vincent Fraisier, Aurélien Roux, Patricia Bassereau, Frédérique Gaits-Iacovoni, Bernard Payrastre, Jocelyn Laporte, Jean-Baptiste Manneville, Bruno Goud (2014 May 19)

BIN1/M-Amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin.

Nature communications : 5647 : DOI : 10.1038/ncomms6647 En savoir plus
Résumé

Phosphoinositide play a central role in physiological processes by Many Assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How is this recruitment Coordinated in space and time is not well Understood. Here we show That BIN1 / M-Amphiphysin2, a protein Involved in T-tubule biogenesis in muscle cells and frequently mutated in centronuclear myopathies, clusters PtdIns (4,5) P2 to recruit ict downstream partner dynamin. By using Several mutants associated with centronuclear myopathies, we find that N-BAR and the SH3 domains of BIN1 control the kinetics and the accumulation of dynamin we membranes, respectively. We that show phosphoinositide Clustering is a mechanism shared by –other That proteins interact with PtdIns (4,5) P2, do not aim to contain a BAR domain. Our numerical simulations Point Out That clustering is a diffusion-driven process in which molecules are not sequestered phosphoinositide. We propose That this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins.

Replier
Deforet M, Hakim V, Yevick HG, Duclos G, Silberzan P (2014 May 6)

Emergence of collective modes and tri-dimensional structures from epithelial confinement.

Nat Commun5:3747 : DOI : 10.1038/ncomms4747 En savoir plus
Résumé

Many in vivo processes, including morphogenesis or tumour maturation, involve small populations of cells within a spatially restricted region. However, the basic mechanisms underlying the dynamics of confined cell assemblies remain largely to be deciphered and would greatly benefit from well-controlled in vitro experiments. Here we show that confluent epithelial cells cultured on finite population-sized domains, exhibit collective low-frequency radial displacement modes as well as stochastic global rotation reversals. A simple mathematical model, in which cells are described as persistent random walkers that adapt their motion to that of their neighbours, captures the essential characteristics of these breathing oscillations. As these epithelia mature, a tri-dimensional peripheral cell cord develops at the domain edge by differential extrusion, as a result of the additional degrees of freedom of the border cells. These results demonstrate that epithelial confinement alone can induce morphogenesis-like processes including spontaneous collective pulsations and transition from 2D to 3D.

Replier
Volker Bormuth, Jérémie Barral, Jean-François Joanny, Frank Jülicher, Pascal Martin (2014 May 5)

Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear.

Proceedings of the National Academy of Sciences of the United States of America : 7185-90 : DOI : 10.1073/pnas.1402556111 En savoir plus
Résumé

Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force-displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell’s characteristic frequency of responsiveness.

Replier
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.

Replier
Thomas Bornschlögl, Patricia Bassereau (2014 Apr 23)

The sense is in the fingertips: The distal end controls filopodial mechanics and dynamics in response to external stimuli.

Communicative & integrative biology : e27341 : DOI : 10.4161/cib.27341 En savoir plus
Résumé

Small hair-like cell protrusions, called filopodia, often establish adhesive contacts with the cellular surroundings with a subsequent build up of retraction force. This process seems to be important for cell migration, embryonic development, wound healing, and pathogenic infection pathways. We have shown that filopodial tips are able to sense adhesive contact and, as a consequence, locally reduce actin polymerization speed. This induces filopodial retraction via forces generated by the cell membrane tension and by the filopodial actin shaft that is constantly pulled rearwards via the retrograde flow of actin at the base. The tip is also the weakest point of actin-based force transduction. Forces higher than 15 pN can disconnect the actin shaft from the membrane, which increases actin polymerization at the tip. Together, this points toward the tip as a mechano-chemical sensing and steering unit for filopodia, and it calls for a better understanding of the molecular mechanisms involved.

Replier
Reffay M, Parrini MC, Cochet-Escartin O, Ladoux B, Buguin A, Coscoy S, Amblard F, Camonis J, Silberzan P (2014 Apr 16)

Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells

Nat Cell Biol16(4):382 : DOI : 10.1038/ncb2917 En savoir plus
Résumé

The leading front of a collectively migrating epithelium often destabilizes into multicellular migration fingers where a cell initially similar to the others becomes a leader cell while its neighbours do not alter. The determinants of these leader cells include mechanical and biochemical cues, often under the control of small GTPases. However, an accurate dynamic cartography of both mechanical and biochemical activities remains to be established. Here, by mapping the mechanical traction forces exerted on the surface by MDCK migration fingers, we show that these structures are mechanical global entities with the leader cells exerting a large traction force. Moreover, the spatial distribution of RhoA differential activity at the basal plane strikingly mirrors this force cartography. We propose that RhoA controls the development of these fingers through mechanical cues: the leader cell drags the structure and the peripheral pluricellular acto-myosin cable prevents the initiation of new leader cells.

Replier
Shalin H Naik, Ton N Schumacher, Leïla Perié (2014 Apr 15)

Cellular barcoding: a technical appraisal.

Experimental hematology : 598-608 : DOI : 10.1016/j.exphem.2014.05.003 En savoir plus
Résumé

Cellular barcoding involves the tagging of individual cells of interest with unique genetic heritable identifiers or barcodes and is emerging as a powerful tool to address individual cell fates on a large scale. However, as with many new technologies, diverse technical and analytical challenges have emerged. Here, we review those challenges and highlight both the power and limitations of cellular barcoding. We then illustrate the contribution of cellular barcoding to the understanding of hematopoiesis and outline the future potential of this technology.

Replier
Ayako Yamada, Alexandre Mamane, Jonathan Lee-Tin-Wah, Aurélie Di Cicco, Coline Prévost, Daniel Lévy, Jean-François Joanny, Evelyne Coudrier, Patricia Bassereau (2014 Apr 7)

Catch-bond behaviour facilitates membrane tubulation by non-processive myosin 1b.

Nature communications : 3624 : DOI : 10.1038/ncomms4624 En savoir plus
Résumé

Myosin 1b is a single-headed membrane-associated motor actin filaments to That Bind with a catch-hop behavior in response to load. In vivo, myosin 1b is required to form membrane tubules at Both endosomes and the trans-Golgi network. To suit les the link entre thesis Fundamental two properties, here we Investigate the capacity of myosin 1b to extract membrane tubes along bundled actin filaments in a minimum reconstituted system. We that show single-headed non-processive myosin 1b can extract membrane tubes at biologically relevant low density. In contrast to kinesins we do not observe motor accumulation at the tip, Suggesting que la Underlying mechanism for tube formation is different. In our theoretical model, myosin 1b catch-bond properties Facilitate tube extraction under the conditions of membrane voltage by Increasing Reducing the density of myo1b required to pull tubes.

Replier
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.

Replier
François Quemeneur, Jon K Sigurdsson, Marianne Renner, Paul J Atzberger, Patricia Bassereau, David Lacoste (2014 Mar 24)

Shape matters in protein mobility within membranes.

Proceedings of the National Academy of Sciences of the United States of America : 5083-7 : DOI : 10.1073/pnas.1321054111 En savoir plus
Résumé

The lateral mobility of proteins within cell membranes is usually thought to be dependent on their size and modulated by local heterogeneities of the membrane. Experiments using single-particle tracking on reconstituted membranes demonstrate that protein diffusion is significantly influenced by the interplay of membrane curvature, membrane tension, and protein shape. We find that the curvature-coupled voltage-gated potassium channel (KvAP) undergoes a significant increase in protein mobility under tension, whereas the mobility of the curvature-neutral water channel aquaporin 0 (AQP0) is insensitive to it. Such observations are well explained in terms of an effective friction coefficient of the protein induced by the local membrane deformation.

Replier
Patricia Bassereau, Benoit Sorre, Aurore Lévy (2014 Mar 18)

Bending lipid membranes: experiments after W. Helfrich’s model.

Advances in colloid and interface science : 47-57 : DOI : 10.1016/j.cis.2014.02.002 En savoir plus
Résumé

Current description of biomembrane mechanics for a large part originates from W. Helfrich’s model. Based On His continuum theory, Many experiments-have-been Performed in the past four Decades membranes is simplified in order to Characterize the mechanical properties of lipid membranes and the contribution of polymers or proteins. The long-term goal Was to Develop a better understanding of the mechanical properties of cell membranes. In this paper, we will review experimental representative Approaches That Were Developed During this period and the hand results That Were therefor obtained.

Replier
G Duclos, S Garcia, H G Yevick, P Silberzan (2014 Mar 14)

Perfect nematic order in confined monolayers of spindle-shaped cells.

Soft matter : 10 : 2346-53 : DOI : 10.1039/c3sm52323c En savoir plus
Résumé

Elongated, weakly interacting, apolar, fibroblast cells (mouse fibroblasts NIH-3T3) cultured at confluence align together, forming large domains (correlation length ∼ 500 μm) where they are perfectly ordered. We study the emergence of this mesoscopic nematic order by quantifying the ordering dynamics in a two-dimensional tissue. Cells are initially very motile and the monolayer is characterized by anomalous density fluctuations, a signature of far-from-equilibrium systems. As the cell density increases because of proliferation, the cells align with each other forming these large oriented domains while, at the same time, the cellular movements and the density fluctuations freeze. Topological defects that are characteristic of nematic phases remain trapped at long times thereby preventing the development of infinite domains. When confined within adhesive stripes of given widths (from 30 μm to 1.5 mm) cells spontaneously align with the domain edges. This orientation then propagates toward the pattern center. For widths smaller than the orientation correlation length, cells perfectly align in the direction of the stripe. Experiments performed in cross-shaped patterns show that in the situation of two competing populations, both the number of cells and the degree of alignment impact the final orientation.

Replier
Sophie Aimon, Andrew Callan-Jones, Alice Berthaud, Mathieu Pinot, Gilman E S Toombes, Patricia Bassereau (2014 Jan 27)

Membrane shape modulates transmembrane protein distribution.

Developmental cell : 212-8 : DOI : 10.1016/j.devcel.2013.12.012 En savoir plus
Résumé

ALTHOUGH membrane shape varies Greatly Throughout The cell, the contribution of membrane curvature to transmembrane protein targeting is unknown Because of the Mechanisms That Numerous sorting take up CONCURRENTLY in cells. To isolate the effect of membrane shape, we used cell-sized unilamellar giant vesicles (GUVs) Containing Either the potassium channel KvAP or the water channel AQP0 membrane to form nanotubes with controlled radii. Whereas the AQP0 concentrations in flat and curved membranes Were indistinguishable, KvAP Was enriched in the tubes, with Greater enrichment in more highly curved membranes. Fluorescence recovery after-photobleaching measurements Showed That Could Both proteins diffuse freely through the neck tube and entre les GUV, and the effect of Each protein is membrane shape and stiffness Was caractérisé using a thermodynamic model sorting. This study Establishes the importance of membrane shape for targeting transmembrane proteins and Provides a method for Determining the actual shape and flexibility of membrane proteins.

Replier