(485h) Microscale Impinging Flow as a Model for Atherosclerosis

Impinging flow in the vascular system is found in non-diseased states, at bifurcations and in long curved vessels, and in the pathological state of stenosed vessels. These are also the most prevalent regions of the vascular system for the progression of atherosclerosis. Atherosclerosis, initially considered a disease of arterial lipid deposition, is now viewed as a disease of chronic inflammation where luminal thickening is accelerated by leukocyte accumulation. Several studies have examined the molecular mechanisms responsible for the progression of atherosclerotic lesion formation, which have led to therapeutic advances in its treatment. However, what is lacking is a holistic understanding of the biophysical mechanisms involved in the progression of this disease.

This study examines the roles of hydrodynamic coupling vs. convection on the biophysics of cell-wall and cell-cell interactions, and how they affect the rate of leukocyte recruitment and rolling in an impinging flow field. To do this, we developed novel in vitro and in silico methods to recreate leukocyte adhesion and rolling in an impinging flow field. An impinging flow chamber was designed to model the microscale flow field of arterial bifurcations. This new impinging flow chamber produces the local fluid streamlines of flow separation near a stagnation point in Stokes flow. Leukocyte adhesion and rolling occurs in the impinging flow chamber as a result of coating P-selectin on the chamber surface. P-selectin is expressed on activated endothelial cells that line the lumen of blood vessels, and its receptor, P-selectin glycoprotein ligand-1 (PSGL-1), is constitutively expressed on leukocytes. A parallel version of Multiparticle Adhesive Dynamics (pMAD) for use on a distributed-memory super computer, which incorporates the microscale flow field found in arterial bifurcations, has also been developed. Parallelization of these simulations is necessary to efficiently handle the computational demands of simulating multiple interacting blood cells.

We have mapped out the near wall x- and y- velocity components of the impinging flow chamber's flow field using 1.9 micrometer diameter fluorescent tracer beads. The near-wall velocity field, local to the stagnation point, shows good agreement with Heimenz's solution for 2-D plane impinging flow. Hence, Heimenz's solution for 2-D plane impinging flow can be used as the external flow field entered into pMAD. To quantify the rate of P-selectin mediated adhesion and rolling human leukocytes are perfused through the impinging flow chamber. These experiments compliment theoretical predictions of cell adhesion and rolling as calculated with pMAD, with the parameters of interest being the number of adherent cells, and the average rolling velocity, as a function of the volume fraction of leukocytes. Finally, pMAD has been used to quantify the relative roles of hydrodynamic coupling and convective flow on adhesion and rolling in impinging flow regions of the vascular system.