Physical and Mechanobiological Basis of Biological Functions of Platelets

Platelets play a unique role in thrombosis and hemostasis. Historical research has revealed biological mechanisms underlying various platelet functions. However, unraveling the complex mechanisms underlying various platelet functions is challenging. Recent progress in high-performance computer has enabled an understanding of the complex biological functions of platelets through combinations of basic principles of physics, such as Newton's laws of motion, fluid mechanics, and mechanobiology. Platelets are blood cells with diameters of 2 to 5 µm. They lack nuclei but contain organelles such as mitochondria. Platelets promptly adhere to the sites of endothelial damage for hemostasis. Adherent platelets are activated to allow plasma ligands of fibrinogen and von Willebrand factor (VWF) to bind stably to them. They also enhance local coagulant activity through their procoagulant activity. The specific biological functions of platelets are mediated by dynamic structural changes in their membrane proteins. Even lipids and proteins that mediate the specific functions of platelets are constructed from atoms following basic physical rules, such as Newton's laws of motion. Thus, the various biological functions of platelets can be constructed from physical principles, starting with the movement of atoms. Here, various complex biological functions of platelets were constructed using mathematical models and simple physical principles. This framework may help explain the complex pathophysiological mechanisms underlying the VWF-platelet interaction in both healthy and diseased conditions. Detailed quantitative biological experiments confirmed the validity of these mathematical models. The future direction of constructive "theoretical medicine and biology," starting from atomic movements, is expected to follow.