Dynamic force spectroscopy of DNA hairpins. I. Force kinetics and free energy landscapes

TL;DR

This study combines theoretical modeling and optical tweezers experiments to analyze the force-dependent folding/unfolding kinetics and free energy landscape of DNA hairpins, providing insights into their thermodynamics and energy barriers.

Contribution

It introduces a simplified model for force-dependent rates and demonstrates how to extract free energy landscape parameters from rupture force experiments.

Findings

Determined the free energy landscape parameters of DNA hairpins.

Validated the theoretical model with experimental rupture force data.

Estimated the zero-force free energy of hairpin formation.

Abstract

We investigate the thermodynamics and kinetics of DNA hairpins that fold/unfold under the action of applied mechanical force. We introduce the concept of the molecular free energy landscape and derive simplified expressions for the force dependent Kramers-Bell rates. To test the theory we have designed a specific DNA hairpin sequence that shows two-state cooperative folding under mechanical tension and carried out pulling experiments using optical tweezers. We show how we can determine the parameters that characterize the molecular free energy landscape of such sequence from rupture force kinetic studies. Finally we combine such kinetic studies with experimental investigations of the Crooks fluctuation relation to derive the free energy of formation of the hairpin at zero force.