Nonlinear Dynamic Force Spectroscopy

TL;DR

This paper extends dynamic force spectroscopy theory to handle nonlinear force responses from polymers and bio-complexes, validated through Monte Carlo simulations, enabling more accurate analysis of complex biological interactions.

Contribution

The authors develop a nonlinear DFS theory compatible with traditional linear models, applicable to polymers with nonlinear force responses, validated by numerical simulations.

Findings

Nonlinear DFS accurately predicts rupture forces in simulated systems.

The theory accommodates polymers with worm-like chain properties.

A protocol for experimental data analysis to estimate bond parameters.

Abstract

Dynamic force spectroscopy (DFS) is an experimental technique that is commonly used to assess information of the strength, energy landscape, and lifetime of noncovalent bio-molecular interactions. DFS traditionally requires an applied force that increases linearly with time so that the bio-complex under investigation is exposed to a constant loading rate. However, tethers or polymers can modulate the applied force in a nonlinear regime. For example, bacterial adhesion pili and polymers with worm-like chain properties are examples of structures that show nonlinear force responses. In these situations, the theory for traditional DFS cannot be readily applied. In this work we expand the theory for DFS to also include nonlinear external forces while still maintaining compatibility with the linear DFS theory. To validate the theory we modeled a bio-complex expressed on a stiff, an elastic and a worm-like chain polymer, using Monte Carlo methods, and assessed the corresponding rupture force spectra. It was found that the nonlinear DFS (NLDFS) theory correctly predicted the numerical results. We also present a protocol suggesting an experimental approach and analysis method of the data to estimate the bond length and the thermal off-rate.