How Mechanical Force Triggers Blood Clotting at the Molecular Scale

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Micrographs from an experiment using the fluorescence biomembrane force probe to interrogate a single molecule on a live platelet. The epifluorescence images (pseudo-colored to reflect the calcium level) of the platelet are superimposed onto the bright-field images. The upper panel shows a platelet with low calcium inside. The lower panel shows calcium firing in the platelet. (Credit: Lining (Arnold) Ju)

Researchers Lining (Arnold) Ju, Cheng Zhu (seated) and Yunfeng Chen are shown with the single-molecule force measurement tool used to study how platelets sense the mechanical forces they encounter during bleeding. (Credit: John Toon, Georgia Tech)

A platelet interacts with the injured vascular surface at the beginning of blood clotting. The platelet uses a glycoprotein molecule to bind von Willebrand factor (VWF) to resist the dislodging force from the bloodstream. The force unfolds the domain of the molecule that binds VWF, which prolongs binding and promotes unfolding of the domain of the molecule that is close to the platelet membrane. These cooperative unfolding events lead to strong calcium signaling inside the platelet. (Credit: Yunfeng Chen, Georgia Tech)