Kinetic And Thermodynamic Modelling Of The
Von Willebrand Factor Mediated Bonds During
Platelet Adhesion Under Flow Conditions
Author(s)
M. Machin, A. Santomaso, M. Mazzucato & P. Canu
Abstract
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 thermodynamics 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, kon and koff.
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
kon/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.
Keywords: platelets, kinetics, association and dissociation rate constant,
residence time, thermodynamics, adhesion equilibrium constant, image analysis.
Keywords
platelets, kinetics, association and dissociation rate constant,
residence time, thermodynamics, adhesion equilibrium constant, image analysis.
Related Book
Other papers in this volume
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