Single-molecule force spectroscopy: Practical limitations beyond Bell's model

TL;DR

This paper develops a maximum likelihood method for analyzing single-molecule force spectroscopy data, identifying the limits of reliably estimating key parameters of the force-dependent escape rate from experimental force distributions.

Contribution

It introduces an optimal maximum likelihood approach for interpreting force spectroscopy data and determines the maximum number of parameters that can be reliably estimated from experimental data.

Findings

Maximum of three parameters can be reliably estimated from data.

The first two parameters are insensitive to the barrier decrease model.

The barrier height estimate depends strongly on the assumed barrier decrease mode.

Abstract

Single-molecule force spectroscopy experiments, as well as a number of other physical systems, are governed by thermally activated transitions out of a metastable state under the action of a steadily increasing external force. The main observable in such experiments is the distribution of the forces, at which the escape events occur. The challenge in interpreting the experimental data is to relate them to the microscopic system properties. We work out a maximum likelihood approach and show that it is the optimal method to tackle this problem. When fitting actual experimental data it is unavoidable to assume some functional form for the force-dependent escape rate. We consider a quite general and common such functional form and demonstrate by means of data from a realistic computer experiment that the maximum number of fit parameters that can be determined reliably is three. They are related to the force-free escape rate and the position and height of the activation barrier. Furthermore, the results for the first two of these fit parameters show little dependence on the assumption about the manner in which the barrier decreases with the applied force, while the last one, the barrier height in the absence of force, depends strongly on this assumption.