Role of Integrin in Cellular Mechanotransduction

Abstract

Chemical and physical cues from the extracellular matrix (ECM) are used as input for an integrated mechanochemical sensory system that controls cell behavior. Forces derived from the ECM have been implicated in various biological systems, including mesenchymal stem cell differentiation and tumor growth. Integrin transmembrane receptors connect the ECM network to the intracellular actomyosin network and are expected to play an important role in force sensing. Our group has previously shown that switching between two different integrin heterodimers ([alpha]5[beta]1 vs [alpha]v[beta]3), that bind the same ECM protein (fibronectin), causes remarkably distinct actin cytoskeletal organization. To investigate the role of these integrins in cellular mechanotransduction, we used fibronectin coated polyacrylamide substrates with varying rigidities and micropillar arrays. Data obtained thus far point to distinct rigidity thresholds for spreading and different distribution of ECM pulling forces for cells expressing either of these integrins. In order to further unravel the role of these integrins in cellular mechanotransduction we developed cyclic substrate stretcher technology coupled to real time confocal imaging.