Interpretations of Receptor–Ligand Dissociation Kinetics from Single-Molecule Pulling Experiments

Abstract

The kinetic response of receptor–ligand bonds to externally imposed force is of essential importance for adhesion-mediated behaviors of cells. Two prevailing experimental approaches, so-called dynamic force spectroscopy and force clamp assay, have been commonly adopted to probe the force dependence of bond dissociation rate at single-molecule level. This study focuses on the outstanding theoretical issue concerning the distinct loading paths and different procedures to extract the kinetic information in the two types of experiments. To address the issue, Monte Carlo simulations have been performed to simulate bond dissociation as a well-to-barrier escape process under dynamically imposed force as well as thermal fluctuations, and the consistency of quantitative interpretations on force-dependent bond lifetimes from the different approaches is examined. Our numerical results show that all the interpretations from different methods collapse into a single master curve of lifetime–force relation for receptor–ligand bonds with slip behavior. However, for bonds with biphasic catch–slip behavior, a procedure based on a Gaussian approximation of rupture force distributions, proposed by Dudko for dynamic force spectroscopy, tends to underestimate bond lifetime for certain force range.