Multivalent Systems of Catch Bonds Exhibit Ideal Bond Behavior

Abstract

Catch bonds play a critical role in the phenomenon of leukocyte rolling and adhesion. All selectin isoforms have been shown to form catch-slip bonds with their ligands, and in vivo presumably act as systems of several parallel receptor-ligand bonds. Little is known, however, about how the unusual kinetics of the catch bond manifest as systems, nor how the inherent compliance of the molecules themselves alters the behavior of the system. We conducted Monte Carlo simulations and derived a closed form probabilistic expression for mean bond lifetime based on reliability theory. Both approaches were based on a single model that included the variables of contact area between the opposing surfaces, molecular compliance, and site density, and allowed for the formation of new bonds when receptors and ligands were within range. We found that at high numbers of initial bound receptor-ligand pairs (≥10) and at low molecular stiffness (≤ 1 pN/nm) receptor-ligand clusters behave exhibit “ideal” behavior over the 0-40 pN range - that is, an overall bond lifetime that is invariant with load. This is in agreement with recent experimental data that found ideal bond behavior at high surface densities of E-selectin. The bond lifetimes even at high site densities were reasonable and not orders of magnitude higher than single bonds. In contrast, slip bond (classical Bell model) interactions give rise to disproportionate increases in bond lifetime with bond on-rate; increasing the on-rate 50 to 75 fold increased mean bond lifetime 100 and 1000 fold respectively. The compliance of the receptor-ligands pairs also exerts a strong influence by modulating the contact area between the surfaces. Our results suggest that classical slip bonds alone are untenable for adhesion in biological systems where cells must move relative to one another.