L-selectin-mediated leukocyte tethering in shear flow is controlled by
multiple contacts and cytoskeletal anchorage facilitating fast
rebinding events

U. S. Schwarz and R. Alon

Proc. Natl. Acad. Sci. USA 101: 6940-6945 (2004)

L-selectin-mediated tethers result in leukocyte rolling only above a
threshold in shear. Here we present biophysical modeling based on
recently published data from flow chamber experiments, which supports
the interpretation that L-selectin-mediated tethers below the shear
threshold correspond to single L-selectin carbohydrate bonds
dissociating on the time scale of milliseconds, whereas
L-selectin-mediated tethers above the shear threshold are stabilized
by multiple bonds and fast rebinding of broken bonds, resulting in
tether lifetimes on the time scale of 10-1 seconds. Our calculations
for cluster dissociation suggest that the single molecule rebinding
rate is of the order of 104 Hz. A similar estimate results if
increased tether dissociation for tail-truncated L-selectin mutants
above the shear threshold is modeled as diffusive escape of single
receptors from the rebinding region due to increased mobility.  Using
computer simulations, we show that our model yields first-order
dissociation kinetics and exponential dependence of tether
dissociation rates on shear stress. Our results suggest that multiple
contacts, cytoskeletal anchorage of L-selectin, and local rebinding of
ligand play important roles in L-selectin tether stabilization and
progression of tethers into persistent rolling on endothelial
surfaces.