Quantitative structural mechanobiology of platelet-driven blood clot contraction.

Quantitative structural mechanobiology of platelet-driven blood clot contraction.
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DOI:
10.1038/s41467-017-00885-x
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发表时间:
2017-11-02
影响因子:
16.6
通讯作者:
Weisel JW
Weisel JW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kim OV;Litvinov RI;Alber MS;Weisel JW

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血凝块收缩在预防出血和血栓性疾病中起着重要作用。在这里,我们揭示和量化在单个血小板水平的凝块收缩的结构机制。收缩的一个关键的基本步骤是附着在纤维蛋白纤维上的血小板丝状伪足的连续伸展-收缩。与细胞沿着纤维迁移的其他细胞基质系统不同,这种“手拉手”的纵向拉伸导致血小板附着的纤维缩短和弯曲,从而形成纤维扭结。当血小板附着在多根纤维上时,血小板通过将纤维横向拉向其纵轴而使纤维蛋白网络致密。单个血小板和聚集体使用肌动球蛋白收缩机制和整合素介导的粘附来重塑细胞外基质,诱导纤维蛋白压实成与活化血小板紧密相关的束状聚集体。揭示血小板驱动的血凝块收缩机制展示了细胞运动原理的重要生物学新应用。血凝块收缩是一种细胞(病理)生理过程,对伤口愈合、止血和血栓形成至关重要。在这里,作者描述了血小板丝状伪足“手拉手”拉紧纤维蛋白纤维的物理结构机制,将它们压缩成捆绑的团块。
Blood clot contraction plays an important role in prevention of bleeding and in thrombotic disorders. Here, we unveil and quantify the structural mechanisms of clot contraction at the level of single platelets. A key elementary step of contraction is sequential extension–retraction of platelet filopodia attached to fibrin fibers. In contrast to other cell–matrix systems in which cells migrate along fibers, the “hand-over-hand” longitudinal pulling causes shortening and bending of platelet-attached fibers, resulting in formation of fiber kinks. When attached to multiple fibers, platelets densify the fibrin network by pulling on fibers transversely to their longitudinal axes. Single platelets and aggregates use actomyosin contractile machinery and integrin-mediated adhesion to remodel the extracellular matrix, inducing compaction of fibrin into bundled agglomerates tightly associated with activated platelets. The revealed platelet-driven mechanisms of blood clot contraction demonstrate an important new biological application of cell motility principles. Blood clot contraction is a cellular (patho)physiological process essential for wound healing, hemostasis, and thrombosis. Here, the authors describe the physical structural mechanism by which platelet filopodia pull “hand-over-hand” on fibrin fibers to compact them into bundled agglomerates.
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