title: Force-Induced Rupture of a DNA Duplex: From Fundamentals to Force Sensors.
abstract: The rupture of double-stranded DNA under stress is a key process in biophysics and nanotechnology. In this article, we consider the shear-induced rupture of short DNA duplexes, a system that has been given new importance by recently designed force sensors and nanotechnological devices. We argue that rupture must be understood as an activated process, where the duplex state is metastable and the strands will separate in a finite time that depends on the duplex length and the force applied. Thus, the critical shearing force required to rupture a duplex depends strongly on the time scale of observation. We use simple models of DNA to show that this approach naturally captures the observed dependence of the force required to rupture a duplex within a given time on duplex length. In particular, this critical force is zero for the shortest duplexes, before rising sharply and then plateauing in the long length limit. The prevailing approach, based on identifying when the presence of each additional base pair within the duplex is thermodynamically unfavorable rather than allowing for metastability, does not predict a time-scale-dependent critical force and does not naturally incorporate a critical force of zero for the shortest duplexes. We demonstrate that our findings have important consequences for the behavior of a new force-sensing nanodevice, which operates in a mixed mode that interpolates between shearing and unzipping. At a fixed time scale and duplex length, the critical force exhibits a sigmoidal dependence on the fraction of the duplex that is subject to shearing.
authors.affiliation: Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford , South Parks Road, Oxford OX1 3QZ, United Kingdom.|School of Physics, Institute for Research in Fundamental Sciences (IPM) , Tehran 19538-33511, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Mosayebi
authors.affiliation: Rudolf Peierls Centre for Theoretical Physics, University of Oxford , 1 Keble Road, Oxford OX1 3NP, United Kingdom.
authors.forename: Ard A
authors.initials: AA
authors.lastname: Louis
authors.affiliation: Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford , South Parks Road, Oxford OX1 3QZ, United Kingdom.
authors.forename: Jonathan P K
authors.initials: JP
authors.lastname: Doye
authors.affiliation: Rudolf Peierls Centre for Theoretical Physics, University of Oxford , 1 Keble Road, Oxford OX1 3NP, United Kingdom.|Department of Mathematics, Imperial College , 180 Queen's Gate, London SW7 2AZ, United Kingdom.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Ouldridge
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D036103:Nanotechnology / Q000379:methods*; D013057:Spectrum Analysis
chemical_list: D004247:DNA
keywords: DNA nanotechnology; coarse-grained modeling; force spectroscopy; molecular simulation; non-equilibrium chemistry