Rolling adhesion of leukocytes onto cerebral endothelium is essential for initiation of inflammatory response. Leukocyte adhesion begins with specific binding between selectin receptors on endothelial cells and their complementary ligands expressed on the surface of leukocytes. Binding to selectin regulates the capture of leukocytes in the face of dislodging hemodynamic forces during their random encounters with endothelium. The impact of physical chemistry of selectin bonds on rolling velocity of leukocyte is extensively studied in the past. The effect of endothelial stiffness, formed by a highly compliant layer of endothelial cells, on leukocytes rolling is not particularly well documented in the literature. We implemented a computational method to model the specific adhesion of a rolling cell to a linear elastic substrate, when the cell is subjected to a creeping shear flow. The sensitivity of cell rolling velocity to the mechanical stiffness of substrate was studied assuming the substrate is coated with P- or E-selectin receptors at a constant areal density. Results show that the cell rolls with higher average translational velocity on softer substrates coated with E-selectin. The stiffness of substrate coated with P-selectin only has a marginal effect on cellular kinematics. The rigidity sensing mechanism was attributed to the mechanical stability of ligand-receptor bonds formed within the footprint of the rolling cell. 

Mechanistic Aspects of Rigidity Sensing by Blood-Borne Cells

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