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Séminaire MSC
"Matière et Systèmes Complexes"

                      

Lundi 9 février 2009 à 11h30
Bâtiment Condorcet, 4ème étage, salle 454 A.

Xavier Trepat
(
Harvard School of Public Health, Boston)


Cytoskeletal Fragility and Collective Cell Migration

 

Xavier Trepat1,2

 

(1) Biophysics and Bioengineering Unit, University of Barcelona, and Institute for Bioengineering of Catalonia.

(2) Program in Molecular and Integrative Physiological Sciences, Harvard University.

 

 

The abilities of the living cell to deform, to contract, and to remodel underlie a wide range of high level biological processes including polarization, locomotion, invasion, angiogenesis, gene expression, wound healing, and pattern formation.  Current understanding of cell mechanics emphasizes the notion that mechanical forces stiffen the cytoskeleton through passive strain-hardening and signaling-mediated reinforcement. Such stiffening has been proposed to be a protective mechanism to preserve the structural integrity of cells and tissues. In this presentation I will provide evidence to the contrary. Instead of stiffening in response to stretch, cells soften and fluidize. Such fluidization provides the cell with a novel mechanism of mechanoprotection based on fragility and suggests a primitive fact of basic biology: eukaryotes harbor collections of molecular conformations in energy wells deep enough to avoid thermal insult but shallow enough to be selectively responsive to physical forcing.

 

In the second part of the presentation I will address the question of how cells mechanically interact to move as a cohesive group. This question has far-reaching implications for understanding fundamental biological processes such as morphogenesis, tissue healing and tumor metastasis. We developed novel technology to precisely map forces exerted by cells migrating within an epithelial sheet. Using this technology we established that collective motion in the advancing cell sheet results neither from leader cells dragging those behind nor from cells that are individually self-propelled, as is commonly presumed.  Instead, each individual cell, both at the leading edge and well inside the sheet, engages in a global tug-of-war that integrates local force generation into a global state of tensile stress.