Characterizing Integrin Tensions during Platelet Adhesion and Stiffness Sensing.

Abstract

Integrin tensions are important force signals mediating platelet adhesion and contraction, and may also participate in platelet activation in response to substrate stiffness, a process referred as platelet stiffness sensing. Here, we characterized integrin tensions during platelet adhesion and stiffness sensing by simultaneously imaging force signals and associated cellular structures at submicron resolution. Our findings identified two distinct mechanisms governing integrin tension generation in platelets. Actomyosin contraction, regulated by MLCK but not ROCK (contrary to nucleated cells), generates integrin tensions in a focal adhesion (FA)-like pattern at the platelet's central region. Independently, F-actin polymerization, mediated by Rac1 and Arp2/3, produces integrin tensions in a ring-like pattern at the cell periphery. We further tested platelet activation on elastic substrates while imaging or restricting integrin tensions. The results indicate that although substrate stiffness strongly modulates integrin tensions in preactivated platelets, this modulation may not play a primary role in platelet stiffness sensing.