Platelet geometry sensing spatially regulates α-granule secretion to enable matrix self-deposition

Although the biology of platelet adhesionon subendothelial matrix after vascular injury is well characterized, how the matrix biophysical properties affect platelet physiology is unknown. Here we demonstrate that geometric orientation of the matrix itself regulates platelet alpha-granule secretion, a key component of platelet activation. Using protein micro-contact printing, we show that platelets spread beyond the geometric constraints of fibrinogen or collagen micropatterns with <5-mu m features. Interestingly, alpha-granule exocytosis and deposition of the alpha-granule contents such as fibrinogen and fibronectin were primarily observed in those areas of platelet extension beyond the matrix protein micropatterns. This enables platelets to self-deposit additional matrix, provide more cellular membrane to extend spreading, and reinforce platelet-platelet connections. Mechanistically, this phenomenon is mediated by actin polymerization, Rac1 activation, and (alpha parallel to b)beta(3) integrin redistribution and activation, and is attenuated in gray platelet syndrome platelets, which lack alpha-granules, and Wiskott-Aldrich syndrome platelets, which have cytoskeletal defects. Overall, these studies demonstrate how platelets transduce geometric cues of the underlying matrix geometry into intracellular signals to extend spreading, which endows platelets spatial flexibility when spreading onto small sites of exposed subendothelium.