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Quantifying how DNA stretches, melts and changes twist under tension

Nature Physics volume 7, pages 731–736 (2011)Cite this article

Abstract

In cells, DNA is constantly twisted, bent and stretched by numerous proteins mediating genome transactions. Understanding these essential biological processes requires in-depth knowledge of how DNA complies to mechanical stress. Two important physical features of DNA, helical structure and sequence, are not incorporated in current descriptions of DNA elasticity. Here we connect well-defined force–extension measurements with a new model for DNA elasticity: the twistable worm-like chain, in which DNA is considered a helical, elastic entity that complies to tension by extending and twisting. In addition, we reveal hitherto unnoticed stick–slip dynamics during DNA overstretching at ∼65 pN, caused by the loss of base-pairing interactions. An equilibrium thermodynamic model solely based on DNA sequence and elasticity is presented, which captures the full complexity of this transition. These results offer deep quantitative insight in the physical properties of DNA and present a new standard description of DNA mechanics.

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Figure 1: Force-induced strand unpeeling of DNA studied with fluorescence microscopy and force spectroscopy.
Figure 2: DNA unwinding under tension quantified using the twistable worm-like chain (tWLC) model.
Figure 3: Stick–slip dynamics are sequence-dependent and close to equilibrium.
Figure 4: Modelling of force-induced, sequence-specific unpeeling of dsDNA.

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Acknowledgements

We thank J. Gore for communicating his experimental data. We thank M. Depken and C. Broederz for discussions. We thank M. Modesti for the kind gift of the eGFP labelled RPA. This work is part of the research program of the ‘Stichting voor Fundamenteel Onderzoek der Materie (FOM)’, which is financially supported by the ‘Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)’ (N.L., E.J.G.P., G.J.L.W.). P.G. is supported by ATLAS, a European Commission-funded Marie Curie early stage training network. G.J.L.W. is recipient of a VICI grant from the ‘Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)’. U.B. was supported by a KNAW visiting professor grant.

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Author notes

  1. Erwin J. G. Peterman and Gijs J. L. Wuite: These authors contributed equally to this work

Authors and Affiliations

  1. LaserLaB Amsterdam and Department of Physics and Astronomy, VU University, De Boelelaan 1081, 1081 HV, Amsterdam, The Netherlands

    Peter Gross, Niels Laurens, Erwin J. G. Peterman & Gijs J. L. Wuite

  2. Niels Bohr Institute, Blegdamsvej 17, 2100 Copenhagen, Denmark

    Lene B. Oddershede

  3. Laboratoire Nanobiophysique, ESPCI, CNRS UMR Gulliver 7083, 10 rue Vauquelin 75005, Paris, France

    Ulrich Bockelmann

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  1. Peter Gross
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Contributions

P.G. performed experiments, the DNA unwinding modelling and analysis. N.L. performed the DNA unwinding analysis. L.B.O. assisted in the design of the study. U.B. developed the thermodynamical model for DNA unpeeling and assisted in the design of the study. E.J.G.P. and G.J.L.W. designed the study and assisted with the analysis. All the authors contributed to the writing of the paper.

Corresponding authors

Correspondence to Erwin J. G. Peterman or Gijs J. L. Wuite.

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Gross, P., Laurens, N., Oddershede, L. et al. Quantifying how DNA stretches, melts and changes twist under tension. Nature Phys 7, 731–736 (2011). https://doi.org/10.1038/nphys2002

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