The platelet and the biophysical microenvironment: lessons from cellular mechanics.

While the role of platelets in hemostasis is well characterized from a biological perspective, the biophysical interactions between platelets and their mechanical microenvironment are relatively unstudied. The field of cellular mechanics has developed a number of approaches to study the effects of extracellular matrix (ECM)-derived mechanical forces on various cells, and has elucidated that integrin-cytoskeleton-mediated force transduction governs many cellular processes. As platelets adhere and spread via molecular machinery that is similar to that which enables other cells to mechanosense and mechanotransduce forces from their biophysical microenvironment, platelets too are likely governed by the same overarching mechanisms. Indeed, recent platelet mechanobiology studies have revealed that key aspects of platelet physiology and activation are regulated by the mechanical and spatial properties of the ECM microenvironment. At the same time, there are also key differences that make platelets unique in the world of cells-- their size, origin as megakaryocyte fragments, and unique αIIbβ3 integrin-- render their mechanosensing activities particularly interesting. The structurally "simple," anucleate nature of platelets coupled with their high actin concentration (20% of total protein) and integrin density [1] seem to make them ideal for mechanical force generation and transmission. Further studies will enhance our understanding of the role of platelet mechanobiology in hemostasis and thrombosis, potentially leading to new categories of diagnostics that investigate the mechanical properties of clots to determine bleeding risk, as well as therapies that target the mechanotransduction signaling pathway to alter the stability of clots.