Triphasic force dependence of E-selectin/ligand dissociation governs cell rolling under flow

During inflammation, flowing leukocytes tether to and roll on vascular surfaces through the association and dissociation of selectin/ligand bonds. The interactions of P- and L- selectins with their respective ligands exhibit catch-slip bonds, such that increasing force initially prolongs and then shortens bond lifetimes. In addition, catch-slip bonds have been shown to govern L-selectin-mediated cell rolling. Using a flow chamber and biomembrane force probe, we show a triphasic force dependence of E-selectin/ligand dissociation that initially behaves as slip bonds, then transitions to catch bonds, and finally transitions again to slip bonds as the force increases. These transitions govern the velocities of neutrophils, HL-60 cells, and Colo-205 cells rolling on E-selectin, as evidenced by the fact that their velocities exhibited a triphasic force dependence that inversely matched the triphasic lifetime-force relationship. At low forces, slip bonds may also precede catch bonds for interactions of P- and L-selectin with their ligands.