Why platelet mechanotransduction matters for hemostasis and thrombosis.

Mechanotransduction is the ability of cells to "feel" or sense their mechanical microenvironment and integrate and convert these physical stimuli into adaptive biochemical cellular responses. This phenomenon is vital for the physiology of numerous nucleated cell types to affect their various cellular processes. As the main drivers of hemostasis and clot retraction, platelets also possess this ability to sense the dynamic mechanical microenvironments of circulation and convert those signals into biological responses integral to clot formation. Like other cell types, platelets leverage their "hands" or receptors/integrins to mechanotransduce important signals in responding to vascular injury to achieve hemostasis. The clinical relevance of cellular mechanics and mechanotransduction is imperative as pathologic alterations or aberrant mechanotransduction in platelets has been shown to lead to bleeding and thrombosis. As such, the aim of this review is to provide an overview of the most recent research related to platelet mechanotransduction, from platelet generation to platelet activation, within the hemodynamic environment and clot contraction at the site of vascular injury, thereby covering the entire "life cycle" of platelets. Additionally, we describe the key mechanoreceptors in platelets and discuss the new biophysical techniques that have enabled the field to understand how platelets sense and respond to their mechanical microenvironment via those receptors. Finally, the clinical significance and importance of continued exploration of platelet mechanotransduction have been discussed as the key to better understanding of both thrombotic and bleeding disorders lies in a more complete mechanistic understanding of platelet function by way of mechanotransduction.