Fig. 4.
Proposed mechanisms of how substrate stiffness affects platelet activation. Platelet mechanosensing of the microenvironment, which includes heterogeneous fibrin polymer networks of differing mechanical properties, likely starts with the initial adhesive event, during which the resistant substrate force balances the inertial movement of the platelet. (A) A platelet engaging with a relatively soft substrate results in a weak αIIbβ3–fibrinogen interaction and short bond lifetime. (B) A stiffer substrate, however, would provide more resistant force leading to more platelet adhesion and outside-in αIIbβ3 signaling. This in turn, would generate a high acto-myosin–mediated internal balancing force, resulting in more platelet spreading on stiffer substrate. Downstream signals will then further trigger platelet activation, thus up-regulating more αIIbβ3 activation, granule secretion, and PS exposure.