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Cell Migration under Mechanical Constraints (DURACELL)
Start date: Jun 1, 2014, End date: May 31, 2019 PROJECT  FINISHED 

Control of cell migration is crucial for many biological processes. Cells sense mechanical cues to guide their migration. As opposed to passive materials, living cells actively respond to the mechanical stimuli of their environment through the transduction of mechanical information into biochemical signaling events. These responses, particularly to rigidity, include differentiation, migration and alterations in cell-matrix and cell-cell adhesion and thus occur over a wide range of time and length scales. I propose to address the effect of substrate mechanical properties on cell migration using quantitative in vitro methods based on micro-fabrication and micro-mechanical techniques. My main objectives are to:1/ Discover specific mechanisms that guide single cells toward stiffer substrates (a process known as durotaxis), investigate the range of stiffness-sensitive responses and determine the molecular mechanisms based on actin dynamics and cell adhesion assembly. 2/ Characterize the emergence of coordinated cell movements and thus how cells move in concert under external mechanical constraints. In addition to cell-substrate interactions, the role of cell-cell junctions is crucial in the transmission of mechanical signals over the cell population. By analyzing tissue dynamics at both mesoscopic and molecular scales, we hope to unravel how epithelial cell sheets mechanically integrate multiple adhesive cues to drive collective cell migration.3/ Elucidate the role of 3D mechanical environments in collective cell migration. In contrast to migration in 2D, cells in 3D must overcome the biophysical resistance of their surrounding milieu. Based on optical and innovative micro-fabrication techniques to modify the stiffness of 3D scaffolds, we will study its influence on cell migration modes and invasion. The goal of this interdisciplinary project is to understand how cells integrate mechanical adhesive signals to adapt their internal organization and ensure tissue integrity

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