Platelet aggregation at the site of vascular injury is essential in clotting. During this process, platelets are bridged by soluble fibrinogen that binds surface integrin receptors. One mystery in the mechanism of platelet aggregation pertains to how resting platelets ignore soluble fibrinogen, the third most abundant protein in the bloodstream, and yet avidly bind immobile fibrinogen on the surface of other platelets at the primary injury site. We speculate that platelet integrins are mechanosensors that test their ligands across the platelet–platelet synapse. To investigate this model, we interrogate human platelets using approaches that include the supported lipid bilayer platform as well as DNA tension sensor technologies. Experiments suggest that platelet integrins require lateral forces to mediate platelet–platelet interactions. Mechanically labile ligands dampen platelet activation, and the onset of piconewton integrin tension coincides with calcium flux. Activated platelets display immobilized fibrinogen on their surface, thus mediating further recruitment of resting platelets. The distribution of integrin tension was shown to be spatially regulated through two myosin-signaling pathways, myosin light chain kinase and Rho-associated kinase. Finally, we discovered that the termination of integrin tension is coupled with the exposure of phosphatidylserine. Our work reveals the highest spatial and temporal resolution maps of platelet integrin mechanics and its role in platelet aggregation, suggesting that platelets are physical substrates for one another that establish mechanical feedback loops of activation. The results are reminiscent of mechanical regulation of the T-cell receptor, E-cadherin, and Notch pathways, suggesting a common feature for signaling at cell junctions.

中文翻译：

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血小板整合素表现出各向异性的机械传感并利用微微力来调节血小板凝集

血管损伤部位的血小板凝集对于凝血至关重要。在此过程中，血小板通过与表面整联蛋白受体结合的可溶性纤维蛋白原桥接。血小板凝集机制的一个谜团涉及静止的血小板如何忽略可溶性纤维蛋白原（血液中第三多的蛋白质），却又在原发性损伤部位与其他血小板表面狂热地结合了固定的纤维蛋白原。我们推测血小板整合素是一种机械传感器，可以检测它们在整个血小板-血小板突触中的配体。为了研究该模型，我们使用包括支持的脂质双层平台以及DNA张力传感器技术在内的方法对人血小板进行讯问。实验表明，血小板整合素需要侧向力来介导血小板与血小板的相互作用。机械不稳定的配体会抑制血小板的活化，并且微微整联蛋白整合素张力的发生与钙通量相吻合。活化的血小板在其表面上显示出固定的纤维蛋白原，从而介导了静息血小板的进一步募集。整联蛋白张力的分布显示出是通过两个肌球蛋白信号通路，肌球蛋白轻链激酶和Rho相关激酶在空间上调节的。最后，我们发现整联蛋白张力的终止与磷脂酰丝氨酸的暴露有关。我们的工作揭示了血小板整合素力学的最高时空分辨率图及其在血小板聚集中的作用，这表明血小板是彼此之间建立激活的机械反馈回路的物理底物。