Rolling adhesion of leukocytes on soft substrates: Does substrate stiffness matter?

Abstract

Cell rolling on vascular endothelium under hydrodynamic blood flow is critical for realization of many physiological and pathological processes, such as inflammatory response and tumor metastasis. The blood-borne cells are in direct contact with the inner layer of endothelium, formed by a highly compliant layer of endothelial cells. The effect of endothelial stiffness on the adhesion and motion of rolling cells is poorly understood. Inspired by recent in vitro studies, here we implemented a computational method to model the specific adhesion of a rolling cell onto a soft substrate, subjected to a creeping shear flow. The substrate is modeled as an elastic half-space, coated with P- and E-selectin receptors with specific affinity for the complementary ligands located on the moving cell. Of particular importance is to predict the effect of substrate stiffness on cell adhesion and its kinematics and kinetics of motion. Simulation results show that the effect of substrate compliance is minimal when coated with P-selectin. Conversely, the trajectory of rolling cells on E-selectin coated substrates is sensitive to the substrate compliance. This is attributed to the moderation of binding forces applied by the soft substrate which leads to a higher average translational velocity of cells.