Mechanical Shedding of L-Selectin from the Leukocyte Surface: Theory and Experiment

L-selectin-mediated leukocyte rolling is a key initial step in the multistep leukocyte adhesion cascade in blood. We have previously shown that constitutive L-selectin is cleaved from the neutrophil surface during rolling on a sialyl Lewis x-coated planar surface under physiological shear flow without the addition of exogenous stimuli. Based on the experimental work, we have extended the Adhesive Dynamics simulation of L-selectin-mediated cell rolling by incorporating the shear-dependent mechanical shedding of L-selectin. Utilizing the Bell model to describe a shedding rate which presumably increases exponentially with force, we were able to recreate the characteristics of L-selectin-mediated neutrophil rolling observed in flow experiments. First, the rolling velocity was found to increase during rolling due to mechanical shedding of L-selectin. The number of L-selectin shed during rolling depends strongly on the shear stress applied. When most of the L-selectin located on the tips of deformable microvilli was cleaved by force exerted on the L-selectin bonds, the cell detached from the reactive plane to join the free stream as observed in experiments. In summary, we showed through detailed computer simulations that the force-dependent shedding of L-selectin could fully explain the rolling behavior of neutrophils mediated by L-selectin in vitro.