The shear threshold effect for particle adhesion to bioreactive surfaces: influence of receptor and ligand site density

Selectins are cell adhesion molecules that mediate capture and rolling adhesion of white blood cells to vascular walls, an essential component of the inflammatory response. Adhesion through L-selectin requires a hydrodynamic shear stress above a threshold level, a phenomenon known as the shear threshold effect. We have reported that the shear threshold effect can he re-created in cell-free systems, in which microspheres coated with the carbohydrate ligand sialyl Lewis x (sLe/sup x/) are perfused over L-selectin-coated surfaces. This paper extends the use of the cell-free system to determine the concurrent influence of receptor and ligand site density on the shear threshold effect. We find that the shear threshold effect diminishes with increasing levels of either L-selectin or sLe/sup x/. At reduced site densities of either L-selectin or sLe/sup x/, the shear threshold effect is present, with maximal rolling observed at a shear stress of 1.2 dynes/cm/sup 2/. At higher site densities of L-selectin and sLe/sup x/, the shear threshold effect disappears. These results suggest that the shear threshold relies on the formation of low numbers of receptor-ligand bonds.