Kinetic and thermodynamic modelling of the von Willebrand factor mediated bonds during platelet adhesion under flow conditions

Platelet tethering to injured vascular surfaces exposed to rapidly flowing blood relies on the interaction with the adhesive protein von Willebrand factor (VWF). By perfusing blood through a flow chamber and analyzing surface events using a tailored/specific image processing and particle tracking algorithms, we derived non-conventional information, such as deposition and removal rates, supporting kinetics and thennodynamics speculations. Statistical reasoning allowed the formulation of single-event observations into mean-field behaviour, suitable for a macroscopic, clinical scale application. The arrest and release frequencies were quantified through association and dissociation rate constants, k(on) and k(off) Variables influencing the arrival/removal rate were identified and their dependence on different experimental factors is illustrated in detail. It is shown how variation of hydrodynamic forces expressed as wall shear rate can be used to sample adhesion rate and bond resistance, ultimately resulting in different k(on/off) values and equilibrium adhesion constant. The issue of establishing whether multiple bonds are synergistic in opposing tensile stress is addressed. Potentials, applicability and limitations of the proposed characterization of platelet adhesion to VWF-coated surfaces are discussed. Developments in this area of research can considerably help to elucidate important aspects of normal hemostasis and pathological arterial thrombosis.