(148h) In Vitro Measurement and Modelling of Platelet Adhesion on Von-Willebrand-Factor-Coated Surfaces in Channel Flow

Understanding the biophysics of platelet adhesion is a long-standing problem in the study of hemostasis and thrombosis. Blood coagulation is initiated by GPIb and GPIIbIIIa receptors on the platelet surface binding with von Willebrand factors (VWF) on the vascular walls. The facts that each platelet contains multiple copies of such receptors and that GPIb-VWF binding is fast and reversible complicate the reaction kinetics. Thus, a clear distinction must be drawn between the bond-level kinetics, i.e. receptor-ligand binding, and the platelet-level kinetics, i.e. the adhesion and detachment of a platelet from the vessel wall. There has not been a detailed study relating these two phenomena at their associated different length scales. Another challenge is that platelet adhesion is a shear-induced phenomenon. Thus, the accurate modeling must consider the fluid mechanics of blood flow.

In this talk, we introduce a multi-scale model for platelet adhesion in channel flow, which takes into account both the fluid mechanics and the biochemistry. Based on our existing model of the margination of platelets in a cellular suspension, we now consider near-wall platelets interacting with wall-tethered VWFs. Therefore, the concentration distribution of platelets in the cross-flow direction is influenced by red-blood-cell-platelet interactions, platelet-platelet interactions as well as the near-wall binding reactions. Our approach utilizes single molecule measurements of bond-level kinetics and couples them with the platelet effective reactive area determined from simulations. Thus, we are able to obtain platelet-level rate constants to compare with our experimental measurements. We utilize a microfluidic device with VWF-coated surfaces in 50-µm-high channels to mimic the actual flow conditions inside human arterioles. We carefully choose our control variables to be the shear rate, hematocrit, GPIb inhibitor dosage and GPIIbIIIa inhibitor dosage. We demonstrate good agreement between our model and experiments and investigate how the change of flow and platelet properties affect the adhesion process. These findings also provide implications for how platelet defects and abnormal flow conditions influence hemostasis and thrombosis.