Atomic Force Microscopy with Nanoscale Cantilevers Resolves Different Structural Conformations of the DNA Double Helix

Carl Leung*†, Aizhan Bestembayeva†‡, RichardThorogate†, Jake Stinson†‡, Alice Pyne†§, ChristianMarcovich†, Jinling Yang, Ute Drechsler#, MichelDespont#, Tilo Jankowski, Martin Tschöpe, andBart W. Hoogenboom*†‡

^† London Centre for Nanotechnology, University College London, 17−19 Gordon Street, London WC1H 0AH, United Kingdom

^‡ Department of Physics and Astronomy,University College London, Gower Street, London WC1E 6BT, United Kingdom

^§ National Physical Laboratory, Hampton Road, Teddington TW11 0LW, United Kingdom

 École Polytechnique, 91128 Palaiseau Cedex, France

 Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, P. R. China

^# IBM Research Division, Zurich Research Laboratory, Säumerstrasse 4, 8803 Rüschlikon, Switzerland

 JPK Instruments AG, Bouchéstrasse 12, 12435 Berlin, Germany

Nano Lett., Article ASAP

DOI: 10.1021/nl301857p

Publication Date (Web): June 26, 2012

Copyright © 2012 American Chemical Society

Structural variability and flexibility are crucial factors for biomolecular function. Here we have reduced the invasiness and enhanced the spatial resolution of atomic force microscopy(AFM) to visualize, for the first time, different structural conformations of the two polynucleotide strands in the DNA double helix, for single molecules under near-physiological conditions. This is achieved by identifying and tracking the anomalous resonance behavior of nanoscale AFM cantilevers in the immediate vicinity of the sample.