Aim: The molecular mechanism of the unique interaction between platelet membrane glycoprotein Ib (GPIb ) and von Willebrand Factor (VWF), necessary for platelet adhesion under high shear stress, is yet to be clarified.
Aim:Computer simulation is a new method for understanding biological phenomena. In this report, we developed a simple platelet simulator representing platelet adhesion under blood flow conditions. Methods: We generated virtual platelets based on the functions of three key adhesive proteins: glycoprotein (
The interaction between platelets and vessel walls in the primary aggregation of platelets was investigated using kinetic Monte Carlo simulation for the multiscale simulation of thrombus formation. The kinetic Monte Carlo lattice model of a platelet surface with glycoprotein Ibα (GPIbα) localization region was simulated by considering 3 types of events: GPIbα diffusion, GPIbα-von Willebrand factor (vWF) bond formation, and breakage. The formation and breakage model of GPIbα-vWF bonds were constructed to reproduce experimental results. Next, the adhesion force between a platelet and vessel wall was evaluated, and the contribution of GPIbα localization in platelet adhesion was investigated. The adhesion force curves with respect to the distance between the platelet and vessel wall were convex upward. The results showed that when the bond formation probability between GPIbα and vWF was small, the localization of GPIbα had a large effect on the adhesion force between the platelet and the vessel wall.
The roles of erythrocytes on platelet adhesion to von Willebrand factor (VWF) on the vessel wall through their membrane glycoprotein (GP)Ibα under blood flow condition is still to be elucidated. Blood specimens containing fluorescently labeled platelet and native, biochemically fixed, or artificial erythrocytes, at various hematocrits were perfused on a surface of VWF immobilized on the wall at a shear rate of 1,500 s-1. Rates of platelet adhesions were measured in each condition. Computer simulation of platelet adhesion to the VWF on the wall at the same shear rate was conducted by solving governing equations with a finite-difference method on K-computer. The rates of platelet adhesion were calculated at various hematocrits conditions in the computational domain of 100 µm (x-axis) x 400 µm (y-axis) x 100 µm (z-axis). Biological experiments demonstrated the positive correlation between the rates of platelet adhesion and hematocrit values in native, fixed, and artificial erythrocytes. (r=0.992, 0.934, and 0.825 respectively, p<0.05 for all). The computer simulation results supported the hematocrit dependent increase in platelet adhesion rates on VWF (94.3/sec at 10%, 185.2/sec at 20%, and 327.9/sec at 30%, respectively). These results suggest the important contributing role of erythrocytes on platelet adhesion to the VWF. The augmented z-axis fluctuation of flowing platelet caused by the physical presence of erythrocytes is speculated as the cause for hematocrit dependent increase in platelet adhesion.
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