ИСТИНА

Hemostatic reaction of an organism to vascular injury is a complex, systematic biological response meant to prevent bleeding and isolate the damaged part of vasculature from circulatory system. Its primary components are blood platelets and a coagulation network that interact to form the hemostatic plug, a combination of cell aggregate and gelatinous fibrin clot. As a result of vascular disease or inflammation, these systems can also be activated inappropriately leading to a dangerous thrombosis scenario - the key trigger for heart attacks and strokes. Recent studies underline the role of mechanics and hydrodynamics in regulation of these biological processes. During the initial stages of thrombosis in microvessels, the adhesion and aggregation of blood platelets plays a leading role. The balance between platelet adhesion and drag results in a critical threshold behavior in the dynamics of a growing thrombus. Mechanical interactions between platelets, red blood cells and particular proteins in plasma should be considered when developing quantitative computational models. In the present work the multiscale approach is developed for direct simulations of initial of thrombosis. The technique is based on coupling of continuum fluid mechanics (Lattice Boltzmann) with the dynamics of particles by a viscous Stokes-like force. Such approach allows for simulations of the whole blood flows on the scale of individual cells. The key advantage is that this framework explicitly reproduces the dynamics mechano-sensitive multimeric proteins involved in platelet adhesion. The initial stages of thrombus growth were studied under realistic hemodynamic conditions. The model demonstrates platelet aggregation due to endothelial inflammation or injury. The results reveal a possible mechano-biological regulatory mechanism based on the coil-stretch transitions in a plasma protein—von Willebrand factor—that serves as a ligand to platelet adhesive membrane receptors. Several aspects regarding the role of erythrocytes and cell-cell collisions are also discussed. This work was supported by RFBR (19-01-00480) and the Interdisciplinary Scientific and Educational School of Lomonosov Moscow State University “Photonic and Quantum Technologies. Digital Medicine”.