Effect of contact time and force on monocyte adhesion to vascular endothelium

In this study we examined whether monocytic cell attachment to vascular end othelium was affected by elevating shear stress at a constant shear rate. C ontact time, which is inversely related to the shear rate, was fixed and vi scosity elevated with dextran to increase the shear stress (and hence the n et force on the cell) independently of shear rate. At a fixed contact time, tethering frequencies increased, rolling velocities decreased, and median arrest durations increased with increasing shear stress. Rolling and short arrests (<0.2 s) were well fit by a single exponential consistent with adhe sion via the formation of a single additional bond. The cell dissociation c onstant, k(off), increased when the shear stress was elevated at constant s hear rate. Firmly adherent cells arresting for at least 0.2 s were well fit by a stochastic model involving dissociation from multiple bonds. Therefor e, at a fixed contact time and increasing shear stress, bonds formed more f requently for rolling cells resulting in more short arrests, and more bonds formed for firmly arresting cells resulting in longer arrest durations. Po ssible mechanisms for this increased adhesion include greater monocyte defo rmation and/or more frequent penetration of microvilli through steric and c harge barriers.