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High flexibility of DNA on short length scales probed by atomic force microscopy

Nature Nanotechnology volume 1, pages 137–141 (2006)Cite this article

Abstract

The mechanics of DNA bending on intermediate length scales (5–100 nm) plays a key role in many cellular processes, and is also important in the fabrication of artificial DNA structures, but previous experimental studies of DNA mechanics have focused on longer length scales than these. We use high-resolution atomic force microscopy on individual DNA molecules to obtain a direct measurement of the bending energy function appropriate for scales down to 5 nm. Our measurements imply that the elastic energy of highly bent DNA conformations is lower than predicted by classical elasticity models such as the worm-like chain (WLC) model. For example, we found that on short length scales, spontaneous large-angle bends are many times more prevalent than predicted by the WLC model. We test our data and model with an interlocking set of consistency checks. Our analysis also shows how our model is compatible with previous experiments, which have sometimes been viewed as confirming the WLC.

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Figure 1: High-resolution AFM images and tracing.
Figure 2: Checks of equilibrium adsorption and failure of WLC on short length scales.
Figure 3: The non-harmonic elasticity model of equation (1) simultaneously fits many statistical properties of the experimental data.

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Acknowledgements

We thank N. R. Dan, N. H. Dekker, M. Inamdar, R. James, R. D. Kamien, I. Kulic, T. Laurence, R. Lavery, J. Maddocks J. Marko, A. Onufriev, P. Purohit, I. Rouzina, J. M. Schurr, R. Seidel, V. Soghomonian, Z.-G. Wang and Y. Zhang for helpful discussions and correspondence. P.A.W. acknowledges grant support from an NSF graduate fellowship. F.M.-H. acknowledges support from La Fundacien Ramon Areces as a postdoctoral fellow. A.J.S. acknowledges funding from the National Institutes of Health (NIH-GM071552). R.P. and P.A.W. acknowledge the Keck Foundation and NSF Grant CMS-0301657 as well as the NSF-funded Center for Integrative Multiscale Modeling and Simulation. J.W. acknowledges support from NIH grants R01 GM054692 and R01 GM058617. C.D. acknowledges the Stichting voor Fundamenteel Onderzoek der Materie (FOM), which is financially supported by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO). P.N. acknowledges NSF Grant DMR04-04674 and the NSF-funded NSEC on Molecular Function at the Nano/Bio Interface DMR04-25780. J.W., R.P. and P.C.N. acknowledge the hospitality of the Kavli Institute for Theoretical Physics, supported in part by the National Science Foundation under Grant PHY99-07949.

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Authors and Affiliations

  1. Whitehead Institute, Cambridge, 02142, Massachusetts, USA

    Paul A. Wiggins

  2. Kavli Institute of NanoScience, Delft University of Technology, Lorentzweg 1, Delft, 2628, CJ, The Netherlands

    Thijn van der Heijden, Fernando Moreno-Herrero & Cees Dekker

  3. Department of Chemical Engineering, Stanford University, Stanford, 94305, California, USA

    Andrew Spakowitz

  4. Division of Engineering and Applied Science, California Institute of Technology, Pasadena, 91125, California, USA

    Rob Phillips

  5. Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, 60208, Illinois, USA

    Jonathan Widom

  6. Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA

    Philip C. Nelson

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  1. Paul A. Wiggins
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Contributions

P.A.W., T.v.d.H., F.M.-H., C.D. and P.N. contributed to the experimental, theoretical and analysis strategy. T.v.d.H. and F.M.-H. carried out the AFM experiments, and with, C.D. and P.A.W. contributed to the custom image-processing software. P.A.W., T.v.d.H., F.M.-H., C.D. and P.C.N. contributed to the analysis. A.S. contributed the analysis and simulations of nonequilibrium adsorption. P.A.W., R.P., J.W. and P.C.N. contributed to the initial formulation of the hypothesis and its refinement. P.W., T.v.d.H., F.M.-H., A.S., C.D. and P.C.N. contributed to the written and graphical presentation; all authors discussed the results and commented on the manuscript.

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Correspondence to Philip C. Nelson.

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The authors declare no competing financial interests.

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Wiggins, P., van der Heijden, T., Moreno-Herrero, F. et al. High flexibility of DNA on short length scales probed by atomic force microscopy. Nature Nanotech 1, 137–141 (2006). https://doi.org/10.1038/nnano.2006.63

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