Invited Paper BI-TuM1
Multiscale Analysis of Biological Adhesion

Tuesday, October 21, 2008, 8:00 am, Room 202

In biological systems, the number of protein bonds mediating cell contacts varies from a few for tethering leukocytes to vessel walls to more than 105 in mature cell-matrix contacts. The characterization of the response of single bonds to a dynamic force provides insights into the physics of noncovalent bond rupture, but the more biologically relevant situation involves the rupture of multiple bonds between extended surfaces. A fundamental question concerns how adhesion between parallel surfaces bridged by multiple, parallel bonds scales with the physical chemical parameters of the protein-ligand bonds. Here I describe theoretical and experimental investigations of the forced separation of two adhesive surfaces linked via a large number of parallel noncovalent protein-ligand bonds. Specifically, we consider how the adhesive force scales with bond parameters (kinetics and affinities) as a function of dynamic loading. These results show that the separation rate relative to the intrinsic relaxation time of the bonds defines three loading regimes and the general dependence of the adhesion on kinetic or thermodynamic parameters of the bonds. In the “equilibrium regime”, the rupture force asymptotically approaches the “equilibrium rupture force”, which increases linearly with the equilibrium bond energy. In the near-equilibrium regime, the rupture force increases with the separation rate and increasingly correlates with the bond rupture barrier, or the logarithm of the dissociation rate. Far from equilibrium where rebinding is irrelevant, the rupture force varies linearly with the rupture barrier, and hence with the bond rupture barrier. Therefore, the adhesive strength of biological interfaces involving multiple, parallel bonds depends on the loading rate, and the loading conditions in turn determine which molecular parameters scale the strength of the junction.