Control of Platelet Adhesion by Rigidity Sensing at the Surface of Fibrin Clot.

Abstract

Recent evidence suggests that substrate rigidity controls cell adhesion through integrin‐mediated signaling. We have found that binding of soluble fibrinogen to the surface of insoluble fibrin matrix inhibits integrin‐mediated cell adhesion by creating an anti‐adhesive fibrinogen layer. To gain understanding of the mechanism underlying the differential ability of cells to adhere to the naked fibrin gel (rigid substrate) and to the loose fibrinogen layer formed on the surface of fibrin (soft substrate), we examined integrin αIIbβ3‐mediated signaling in platelets. Platelet adhesion to fibrin clots induced strong phosphorylation of FAK and Syk kinases as compared to adhesion on soft substrates. Also, the rigid, but not soft substrate induced recruitment of signaling molecules talin and skelemin to integrin‐containing focal adhesions. Consistent with their limited ability to induce sufficient signaling, soft substrates do not support platelet spreading. Differential platelet signaling was also observed when fibrinogen was adsorbed on plastic at low and high densities, a condition which mimics rigid and soft substrates, respectively. These data suggest that soluble fibrinogen prevents stable platelet adhesion to the fibrin clot by modifying its mechanical properties which results in insufficient signaling and reduced force generation. NIH HL 63199