From Surface Protrusion to Tether Extraction: A Mechanistic Model

Human leukocyte rolling on the endothelium is essential for leukocyte emigration and it is a process regulated by many factors including shear stress, receptor-ligand kinetics, and mechanical properties of cells and molecules. During this process, both leukocytes and endothelial cells (ECs) are pulled by forces due to blood flow and both may experience surface protrusion and tether extraction. In this study, we established a two-scale (cellular and molecular) model of cellular deformation because of a point pulling force and illustrated how surface protrusion makes the transition to tether extraction, either gradually or abruptly. Our simulation results matched well with what was observed in the experiments conducted with the optical trap and the atomic force microscope. We found that, although the traditional method of determining the force loading rate and the protrusional stiffness were still reasonable, the crossover force should not be simply interpreted as the rupture force of the receptor-cytoskeleton linkage. With little modification, this model can be incorporated into any leukocyte rolling model as a module for more accurate and realistic simulation.