Dynamic of cell mechanotransduction – DOCM

Cells ability to sense the mechanical properties of their microenvironment is a critical feature for tissue homeostasis (Jaalouk and Jan Lammerding 2009). Current evidence makes a strong case for a bidirectional relationship between integrin-mediated adhesion and mechanical forces genesis in that process. Classical genetic approaches have pointed out the major role of ß1 and ß3 integrins in cell mechanosensitivity without specifying their relative contribution. However integrin functions highly depend upon their dynamics that is not easily tunable with classical genetic approaches. For instance, how the respective modulations of ß1 and ß3 integrin expression dynamically affect cell force generation remains unravelled. This project aims at designing an innovative multi-parametric platform built around an inverted microscope that will combine time-resolved force measurement at the single cell level and optical tools to both control and measure cell adhesive properties. Firstly, We hereby propose to combine integrin targeting optogenetic and time resolved traction force microscopy (tTFM) to induce dynamic genetic transition on a single cell in order to decipher the respective roles of ß1 and ß3 integrins in cell force generation and rigidity sensing. Secondly, we will analyse integrin-mediated mechanotransduction at the scale of single adhesive structures by combining micropatterned traction force microscopy and multi-ROI-FRAP measurements of integrin mobility. Those two complementary approaches will help us to investigate mechanotransduction through a multiscale dynamic approach. This project will make profit of the unique expertise of the LIPhy team (Grenoble) for instrumental and methodological developments devoted to cellular biomechanics. As a matter of fact these capabilities have attracted collaborators from a biology laboratory (Dysad team IAB, Grenoble) who joined this JCJC project.