HYDRODYNAMIC EFFECTS AND RECEPTOR INTERACTIONS OF PLATELETS AND THEIRAGGREGATES IN LINEAR SHEAR-FLOW

We have modeled platelet aggregation in a linear shear flow by account ing for two body collision hydrodynamics, platelet activation and rece ptor biology. Considering platelets and their aggregates as unequal-si zed spheres with DLVO interactions (psi(platelet) = -15 mV, Hamaker co nstant = 10(-19) J), detailed hydrodynamics provided the flow field ar ound the colliding platelets. Trajectory calculations were performed t o obtain the far upstream cross-sectional area and the particle flux t hrough this area provided the collision frequency. Only a fraction of platelets brought together by a shearing fluid flow were held together if successfully bound by fibrinogen cross-bridging GPIIb/IIIa recepto rs on the platelet surfaces. This fraction was calculated by modeling receptor-mediated aggregation using the formalism of Bell (Bell, G. I. 1979. A theoretical model for adhesion between cells mediated by mult ivalent ligands. Cell Biophys. 1:133-147) where the forward rate of bo nd formation dictated aggregation during collision and was estimated f rom the diffusional limited rate of lateral association of receptors m ultiplied by an effectiveness factor, eta, to give an apparent rate. F or a value of eta = 0.0178, we calculated the overall efficiency (incl uding both receptor binding and hydrodynamics effects) for equal-sized platelets with 50,000 receptors/platelet to be 0.206 for G = 41.9 s(- 1), 0.05 for G = 335 s(-1), and 0.0086 for G = 1920 s(-1), values whic h are in agreement with efficiencies determined from initial platelet singlet consumption rates in flow through a tube. From our analysis, w e predict that bond formation proceeds at a rate of similar to 0.1925 bonds/mu m(2) per ms, which is similar to 50-fold slower than the diff usion limited rate of association. This value of eta is also consisten t with a colloidal stability of unactivated platelets at low shear rat es. Fibrinogen was calculated to mediate aggregation quite efficiently at low shear rates but not at high shear rates. Although secondary co llisions (an orbitlike trajectory) form only a small fraction of the t otal number of collisions, they become important at high shear rates ( >750 s(-1)), as these are the only collisions that provide enough time to result in successful aggregate formation mediated by fibrinogen. T he overall method provides a hydrodynamic and receptor correction of t he Smoluchowski collision kernel and gives a first estimate of eta for the fibrinogen-GPIIb/IIIa cross-bridging of platelets. We also predic t that secondary collisions extend the shear rate range at which fibri nogen can mediate successful aggregation.