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Published July 19, 1990 | public
Journal Article

Atomic-scale imaging of DNA using scanning tunnelling microscopy


THE scanning tunnelling microscope (STM) has been used to visualize DNA under water, under oil and in air. Images of single-stranded DNA have shown that submolecular resolution is possible. Here we describe atomic-resolution imaging of duplex DNA. Topographic STM images of uncoated duplex DNA on a graphite substrate obtained in ultra-high vacuum are presented that show double-helical structure, base pairs, and atomic-scale substructure. Experimental STM profiles show excellent correlation with atomic contours of the van der Waals surface of A-form DNA derived from X-ray crystallography. A comparison of variations in the barrier to quantum mechanical tunnelling (barrier-height) with atomic-scale topography shows correlation over the phosphate-sugar backbone but anticorrelation over the base pairs. This relationship may be due to the different chemical characteristics of parts of the molecule. Further investigation of this phenomenon should lead to a better understanding of the physics of imaging adsorbates with the STM and may prove useful in sequencing DNA. The improved resolution compared with previously published STM images of DNA may be attributable to ultra-high vacuum, high data-pixel density, slow scan rate, a fortuitously clean and sharp tip and/or a relatively dilute and extremely clean sample solution. This work demonstrates the potential of the STM for characterization of large biomolecular structures, but additional development will be required to make such high resolution imaging of DNA and other large molecules routine.

Additional Information

© 1990 Nature Publishing Group. Received 6 February; accepted 23 April 1990. R.J.D. and M.G.Y. are both to be considered as first author. We thank C. Spence and J. Meier of Dr. L. Hood's group for persuading us to undertake this project and for preparing DNA solution. We also thank J. Hurley and M. sud of BioDesign Inc. for providing the molecular modelling software, and Dr. W.A. Goddard III for discussions of this work. R.J.D. is an NIH trainee and M.G.Y. is a Department of Education fellow. This work has been supported by the NIH, ONR and the Shell Companies Foundation.

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