Abstract
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.
Highlights
Blood clot contraction plays an important role in prevention of bleeding and in thrombotic disorders
We pay special attention to the elementary steps of clot contraction in the real-time scale by visualizing single contracting platelets bound to an individual fibrin fiber and their effects on remodeling of the entire fibrin network powered by multiple contracting platelets
When an adherent platelet spread over a single fibrin fiber, its filopodia stretched along the fiber axis (Fig. 1a)
Summary
Blood clot contraction plays an important role in prevention of bleeding and in thrombotic disorders. The revealed platelet-driven mechanisms of blood clot contraction demonstrate an important new biological application of cell motility principles. Non-muscle myosin IIA is critical for platelet contraction by interacting with actin to form a contractile unit similar to other actomyosins in cell motility. While it has been demonstrated that platelets and fibrin are necessary for contraction of clots, which has been studied at different special scales from a whole clot to the singlecell level[11,12,13,14,15,16], much less is known about how individual platelets or small platelet aggregates exert contractile force on individual fibrin fibers and how this tension causes collapse of the entire filamentous network and reduction of clot volume. We discover a structural mechanism by which local platelet-fibrin interactions result in dramatic modifications of the whole clot architecture
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