Rebinding kinetics from single-molecule force spectroscopy experiments close to equilibrium

TL;DR

This paper extends the analysis of single-molecule force spectroscopy data by incorporating rebinding kinetics, providing new theoretical tools and estimators to better understand bond dynamics near equilibrium.

Contribution

It introduces an augmented theory accounting for rebinding, with approximate solutions and efficient estimators, enhancing the analysis of force spectroscopy experiments.

Findings

Developed approximate analytic solutions for rebinding kinetics.

Created maximum likelihood estimators for force-dependent rates.

Provided open-source implementation and validated with synthetic data.

Abstract

Analysis of bond rupture data from single-molecule force spectroscopy experiments commonly relies on the strong assumption that the bond dissociation process is irreversible. However, with increased spatiotemporal resolution of instruments it is now possible to observe multiple unbinding-rebinding events in a single pulling experiment. Here, we augment the theory of force-induced unbinding by explicitly taking into account rebinding kinetics, and provide approximate analytic solutions of the resulting rate equations. Furthermore, we use a short-time expansion of the exact kinetics to construct numerically efficient maximum likelihood estimators for the parameters of the force-dependent unbinding and rebinding rates, which pair well with and complement established methods, such as the analysis of rate maps. We provide an open-source implementation of the theory, evaluated for Bell-like rates, which we apply to synthetic data generated by a Gillespie stochastic simulation algorithm for time-dependent rates.