Blood Rheology and Leukocyte Mechanics

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DESCRIPTION (provided by applicant): Physical contact between circulating cells and the vessel wall is of central importance in immune surveillance, metastasis and atherosclerosis. But little is known about the mechanical interactions between adhering leukocytes and the red blood cells that constitute most of the blood volume. We have recently discovered that red blood cells (RBCs) play an important role in leukocyte-endothelial (L-E) interactions, both in vitro and in vivo through the unique suspension rheology characteristics that they impart to blood. We found a 10-fold increase in the number of bound leukocytes when the hematocrit of the cell suspension in a flow chamber was increased from 0 to 30%. We have also discovered that this enhancement of cell adhesion in the presence of RBCs is due to physical, rather than chemical interactions between the adherent lymphocytes and RBCs. Although the role of RBCs in platelet deposition onto the vessel wall has been studied extensively, little attention has been given to the role of RBCs in promoting L-E interactions. The proposed study will quantify the physical forces and rheological parameters that cause enhanced L-E interactions in blood flow using both experimental and theoretical approaches. Flow chamber studies will be carried out in the parallel plate flow chamber, a device that allows precise control over flow rates and solution rheology as cells flow through a rectangular chamber. Theoretical studies will employ the Lattice-Boltzmann method, a novel approach we recently adapted to the field of blood rheology and particle interactions. The unique combination of experimental and theoretical approaches will form the basis of my independent scientific career.