Distinct platelet F-actin patterns and traction forces on von Willebrand factor versus fibrinogen
Distinct platelet F-actin patterns and traction forces on von Willebrand factor versus fibrinogen
复制标题
血管性血友病因子与纤维蛋白原的不同血小板 F-肌动蛋白模式和牵引力
DOI：
10.1016/j.bpj.2023.07.006
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发表时间：
2023
影响因子：
3.4
通讯作者：
Thomas, Wendy E.
中科院分区：
文献类型：
--
作者：
Mollica, Molly Y.;Beussman, Kevin M.;Kandasamy, Adithan;Rodríguez, Lesley Martínez;Morales, Francisco R.;Chen, Junmei;Manohar, Krithika;del Álamo, Juan C.;López, José A.;Thomas, Wendy E.
在血管损伤时，血小板通过与内皮下层和彼此结合形成止血栓。血小板-基质结合最初由血管性血友病因子（VWF）介导，血小板-血小板结合主要由纤维蛋白原和VWF介导。结合后，血小板的肌动蛋白细胞骨架驱动其收缩，产生对止血很重要的牵引力。我们对粘附环境、f -肌动蛋白形态和牵引力之间关系的理解是有限的。在这里，我们检查了附着在纤维蛋白原和VWF表面的血小板的f -肌动蛋白形态。我们确定了由这些蛋白质涂层诱导的不同的f -肌动蛋白模式，并发现这些模式通过机器学习可识别为三种类型：固体，结节和空心。我们观察到血小板在VWF上的牵引力明显高于纤维蛋白原涂层，并且这些牵引力随f -肌动蛋白模式而变化。此外，我们分析了血小板中的f -肌动蛋白取向，并注意到它们的细丝在纤维蛋白原涂层上更呈圆周状，具有空心的f -肌动蛋白模式，而它们在VWF上更呈径向状，具有固体的f -肌动蛋白模式。最后，我们注意到牵引力的亚细胞定位与蛋白质包被和f -肌动蛋白模式相对应：vwf结合的固体血小板在其中心区域具有更高的力，而纤维蛋白原结合的空心血小板在其外围具有更高的力。纤维蛋白原和VWF上的这些不同的f -肌动蛋白模式及其在f -肌动蛋白取向、力大小和力定位上的差异可能对止血、血栓结构和静脉与动脉血栓形成有影响。
Upon vascular injury, platelets form a hemostatic plug by binding to the subendothelium and to each other. Platelet-to-matrix binding is initially mediated by von Willebrand factor (VWF) and platelet-to-platelet binding is mediated mainly by fibrinogen and VWF. After binding, the actin cytoskeleton of a platelet drives its contraction, generating traction forces that are important to the cessation of bleeding. Our understanding of the relationship between adhesive environment, F-actin morphology, and traction forces is limited. Here, we examined F-actin morphology of platelets attached to surfaces coated with fibrinogen and VWF. We identified distinct F-actin patterns induced by these protein coatings and found that these patterns were identifiable into three classifications via machine learning: solid, nodular, and hollow. We observed that traction forces for platelets were significantly higher on VWF than on fibrinogen coatings and these forces varied by F-actin pattern. In addition, we analyzed the F-actin orientation in platelets and noted that their filaments were more circumferential when on fibrinogen coatings and having a hollow F-actin pattern, while they were more radial on VWF and having a solid F-actin pattern. Finally, we noted that subcellular localization of traction forces corresponded to protein coating and F-actin pattern: VWF-bound, solid platelets had higher forces at their central region while fibrinogen-bound, hollow platelets had higher forces at their periphery. These distinct F-actin patterns on fibrinogen and VWF and their differences in F-actin orientation, force magnitude, and force localization could have implications in hemostasis, thrombus architecture, and venous versus arterial thrombosis.