(332e) Influence Of Brownian Motion On Blood Platelet Flow Behavior And Adhesive Dynamics Near A Planar Wall

Blood platelets are discoid particles approximately 2 μm diameter in size. At the time of vascular injury, platelets are recruited from the bloodstream to the exposed subendothelial layer at the lesion where they promptly aggregate to seal the wound. The extent of influence of the platelet shape on (1) duration and frequency of cell-surface contact, (2) magnitude of shear forces exerted on these cells when tethered via receptor-ligand bonds to the subendothelial surface at the site of vascular injury, and (3) platelet collision frequency with other blood cells has not been well characterized to date. One reason for the lack of correlation studies between platelet shape and platelet physiological behavior is that solutions for non-spherical particulate flows are much more difficult to obtain compared to that for suspended spheres because of the complexities in determining the hydrodynamic interactions between non-spherical particles or between a non-spherical particle and a bounding surface. Therefore the number of studies that have addressed unactivated (non-spherical) platelet flow and adhesive characteristics in a bounded space is very few. One interesting aspect of blood platelets not yet explored in platelet adhesion/aggregation studies is that these micro-particles fall within the realm of Brownian particles, primarily due to their sub-micron thickness (~ 0.25 μm). It is therefore possible that the Brownian motion of a platelet may significantly influence its flow behavior and adhesive dynamics when bound to a surface or to another platelet.

We used the Platelet Adhesive Dynamics computational method to study the influence of Brownian motion of a blood platelet on its flow characteristics near a surface in the creeping flow regime. The computational method employed in our study for calculating the rigid body motion of an oblate spheroid-shaped particle (platelet) is based on the Completed Double Layer ? Boundary Integral Equation Method (CDL-BIEM), a boundary elements method proposed by Kim an Karilla¹ to solve the integral representation of the Stokes equation. Two important characterizations were done in this regard: (1) quantification of the platelet's ability to contact the surface by virtue of the Brownian forces and torques acting on it, and (2) determination of the relative importance of Brownian motion in promoting surface encounters in the presence of shear flow. We determined the Peclet number for a platelet undergoing Brownian motion in shear flow, which could be expressed as a simple linear function of height of the platelet centroid, H from the surface: Pe (platelet) = γ•(1.56H + 0.66) for H > 0.3 μm, where γ is the linear shear rate in the fluid. Our results demonstrate that at timescales relevant to shear flow in blood, Brownian motion plays an insignificant role in influencing platelet motion or creating further opportunities for platelet-surface contact. The platelet Peclet number at shear rates > 100 s^-1 is large enough (> 200) to neglect platelet Brownian motion in computational modeling of flow in arteries and arterioles for most practical purposes even at very close distances from the surface. We also conducted adhesive dynamics simulations to determine the effects of platelet Brownian motion on GPIbα-vWF-A1 single-bond dissociation dynamics. Brownian motion was found to have little effect on bond lifetime and caused minimal bond stressing as bond rupture forces were calculated to be less than 0.005 pN. We conclude from our results that for the case of platelet-shaped cells, Brownian motion is not expected to play an important role in influencing flow characteristics, platelet-surface contact frequency and dissociative binding phenomena under flow at physiological shear rates (> 50 s^-1).

References:

1. Kim, S.; Karilla, S. J. Microhydrodynamics: Principles and Selected Applications. Butterworth-Heinemann: Stoneham, 1991.