Abstract
Neutrophils roll by reversible binding and unbinding of P-selectin Glycoprotein Ligand-1 (PSGL-1) to P-selectin. The average lifetime of P-selectin—PSGL-1 bonds may increase with applied force until the force reaches a critical value of 11 pN. Here, we apply this "catch bond" behavior and the transition to slip bonds at supercritical forces to study their effect on neutrophil rolling. Leukocyte adhesion significantly depends on cellular deformability, viscoelastic extension of leukocyte microvilli, and membrane tether pulling. We use two custom computational models: ETMA in which the leukocyte is a rigid sphere and Visco-Elastic Cell Adhesion Model (VECAM) in which the leukocyte is a deformable particle. Both models incorporate microvillus viscoelasticity and tether pulling and describe receptor-ligand binding kinetics using a stochastic Monte Carlo approach, with on- and off-rates determined according to the spring model of Dembo. Bonds are characterized by bound state and transition state spring constants, with the latter being higher of the two in the case of catch bonds. Our simulations show that catch bonds lead to firm adhesion of a rigid cell at wall shear stress of 0.5 dyn/cm2, but the transition of these bonds to slip bonds induces stable rolling. Catch bonds favor tether pulling in a deformable cell that eventually results in cell detachment at this subthreshold shear stress. We conclude that catch bonds, tether dynamics and cell deformation all contribute to leukocyte rolling.