Fig. 9

Working model of the Extensional Strain Sensing (\(\dot{\varepsilon}\)-S) Mechanosome. Extensional strain (\(\dot{\varepsilon}\)) generated by flow acceleration and acute changes in platelet trajectory impose a deformational load on the platelet plasma membrane and underlying spectrin-based membrane skeleton engaging the \(\dot{\varepsilon}\)-S mechanosome comprised of [1.] The Sensor—Piezo1 gating driven by deformational stress loading of the plasma membrane and membrane skeleton (membrane tension) leads to low level Ca²⁺ influx; [2.] The Amplifier—Piezo1-mediated Ca²⁺ influx triggers near-membrane ATP release via Pannexin1 (Panx1) triggering subsequent P2X1 activation, amplifying \(\dot{\varepsilon}\)-S [Ca²⁺]_c flux; [3.] The Clutch—A localized pool of PI(3)P, dependent on basal PI3-kinase C2α activity, modulates membrane skeleton composition, membrane elastic deformation, and associated force coupling through the plasma membrane to Piezo1