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New biomimetic systems to study cellular acto-myosin contractility – Contract

contract

New biomimetic systems to study cellular actomyosin <br />contractility

Understand acto-myosin contractility

We aim at understanding some of the basic mechanisms that control the dynamic mechanical properties of cells. These properties are involved in key cellular processes, including shape changes, motility, division, and mechanosensitivity. This project is positioned at the interface between biochemistry and biophysics.

- The actin toolbox: generation of controlled actin structures under geometrical constraints on beads, liposomes, and patterned substrates
- Myosin-based contractility of controlled actin architectures on patterned substrates and underneath the membrane of liposomes.
- Mechanical properties of controlled acto-myosin architectures and the emergence of spontaneous oscillations under load.

Contraction is obtained around liposomes, contractility on patterned surfaces is obtained, motility assay is working.

develop the three assays in collaboration

K. Carvalho, J. Lemière, F. Faqir, J. Manzi, L. Blanchoin, J. Plastino, T. Betz, C. Sykes «Actin polymerization or myosin contraction: two ways to build up cortical tension for symmetry breaking”, en revision à Philosophical Transaction B

L. Blanchoin, R. Boujemaa-Paterski, C. Sykes and J. Plastino “Actin dynamics, architecture and mechanics in cell motility” , en révision à, Physiological Reviews (2013)

Acto-myosin dynamics govern many cellular processes, including motility, shape changes, and spontaneous mechanical oscillations. Contraction in cells is ensured by myosin molecular motors that exert forces on actin filaments. This active process is complex, in part because actin filaments are often dynamic, constantly polymerizing and depolymerizing, which results in the reorganization of the contractile network. Acto-myosin contractility was reproduced in bulk in a test tube three decades ago using cell extracts, and, in parallel, the working mechanism of single myosin motors has been studied extensively over the last twenty years. However, little is known about how the structure of the actin network conditions its contraction, about the detailed mechanism of contraction in an intricate actin structure, about how the network remodels as it contracts, and how spontaneous oscillations can emerge from acto-myosin contraction. To study these fundamental aspects of cell contractility, we propose to develop new in vitro biomimetic systems with actin structures of prescribed geometries. The three partners involved in this proposal will share their know-how in the biochemistry of actin, myosin, and in the design of micro-patterns to control the architecture of actin networks (Blanchoin), in reconstituted systems that produce growth of an actin network from a lipid membrane (Sykes), and in biophysical measurements of forces produced by the interaction of myosin with the actin network (Martin and Sykes).
We aim at
1- Generating biochemically and physically controlled actin structures. We will impose geometrical constraints to the actin network by directing actin polymerization from the surface of beads, of micro-patterns or of liposomes.
2- Characterizing myosin-based contraction in constantly growing actin structures: networks, parallel or anti-parallel actin bundles, or crosslinked filaments.
3- Measuring the mechanical properties of these contractile acto-myosin structures, in particular membrane tension in the case of actin growing from a liposome membrane, and the emergence of spontaneous oscillations under load.
We expect to create shape changes that mimic those observed in cells. Theoretical biophysical modeling and computer simulations will be used to describe our experimental observations. From this interdisciplinary approach, we intend to unveil generic principles that govern cell mechanics as well as the dynamics of cell shape changes and oscillations.

Project coordinator

Madame Cécile Sykes (Institut Curie / CNRS UMR168 / UPMC "Physico-chimie "Curie") – cecile.sykes@curie.fr

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

UMR5168 CEA Direction des sciences du vivant - Laboratoire de Physiologie Cellulaire et Végétale iRTSV : Équipe 05
IC2 Institut Curie / CNRS UMR168 / UPMC "Physico-chimie "Curie"
IC Institut Curie / CNRS UMR168 / UPMC "Physico-chimie "Curie"

Help of the ANR 519,710 euros
Beginning and duration of the scientific project: November 2012 - 36 Months

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