Hydrodynamic effects and receptor interactions of platelets and their aggregates in linear shear flow

Abstract

We have modeled platelet aggregation in a linear shear flow by accounting for two body collision hydrodynamics, platelet activation and receptor biology. Considering platelets and their aggregates as unequal-sized spheres with DLVO interactions (psi(platelet) = -15 mV, Hamaker constant = 10(-19) J), detailed hydrodynamics provided the flow field around the colliding platelets. Trajectory calculations were performed to obtain the far upstream cross-sectional area and the particle flux through 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 receptors 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 multivalent ligands. Cell Biophys. 1:133-147) where the forward rate of bond formation dictated aggregation during collision and was estimated from the diffusional limited rate of lateral association of receptors multiplied by an effectiveness factor, eta, to give an apparent rate. For a value of eta = 0.0178, we calculated the overall efficiency (including 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 which are in agreement with efficiencies determined from initial platelet singlet consumption rates in flow through a tube. From our analysis, we predict that bond formation proceeds at a rate of approximately 0.1925 bonds/microm2 per ms, which is approximately 50-fold slower than the diffusion limited rate of association. This value of eta is also consistent with a colloidal stability of unactivated platelets at low shear rates. Fibrinogen was calculated to mediate aggregation quite efficiently at low shear rates but not at high shear rates. Although secondary collisions (an orbitlike trajectory) form only a small fraction of the total 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. The overall method provides a hydrodynamic and receptor correction of the Smoluchowski collision kernel and gives a first estimate of eta for the fibrinogen-GPIIb/IIIa cross-bridging of platelets. We also predict that secondary collisions extend the shear rate range at which fibrinogen can mediate successful aggregation.

Fluid Shear Regulates the Kinetics and Receptor Specificity of Staphylococcus aureus Binding to Activated Platelets

“…Platelet-S. aureus heteroaggregation in response to hydrodynamic shear exposure is determined by the intercellular collision frequency and the capture efficiency of these collisions (21,32,33). The two-body collision frequency per unit volume, f [(i,j),(m,n)] , is a function of the physical parameters of the experimental system, and can be calculated by the Smoluchowski equation:…”

Aggregation of blood components on a surface in a microfluidic environment

“…Since it would take more than 1 min for a platelet to finish the loop, the residence time of the platelets near the wall is long enough to enhance their adherence after their activation in the predicted 17-34 s. Furthermore, high shear stress will also enhance the activation of platelets near the tubing wall. 17 Once the platelets are activated, they will likely adhere to each other and form aggregates, provided that the flow can create an environment for prolonged contacts between platelets with higher platelet collision frequency ͑which is a function of the volume of particles undergoing shear-induced collisions 18 ͒ due to the increase in the hydrodynamic effective volume ͑HEV͒ of the platelets caused by changes in radii and/or shape produced by activation. The recirculation zones in our loop system are a good example for such environment.…”

The Effect of Convective Flows on Blood Coagulation Processes

“…In particular, accounting for shear stress is essentially important in the analysis of platelet aggregation [12] and simulations of a haemostatic system. The efforts to operate with average values on space (when shear fl ow of blood in a vessel was taken into account) were undertaken in another study [13] .…”