A structural imaging study of single DNA molecules on carbon nanotubes

The structure of DNA has been the subject of intense and continuous study for over 56 years [1, 2, 3]. Studies using electron and x-ray diffraction from crystals of DNA have provided a wealth of structural information on sequences in different conformations [4, 5], but to date individual bases in single DNA molecules have not been resolved [6, 7]. Here we use standard and aberration corrected transmission electron microscopes to image the damaged remnants of individual nucleotides in unlabeled, 30 base-length single-stranded DNA bound to single-walled carbon nanotubes. We resolve the individual atoms in carbon nanotubes at 1.0 Angstrom resolution and 80 keV, which provide a near ideal substrate for the direct imaging of single molecules. From the images, we determine several structural parameters of the damaged molecules on the nanotubes, including length, apparent periodic structure, binding distance, and helical wrapping conformation. We present computer simulated images of nucleotides and polynucleotides that compare favorably to the experimental data [8]. Our results are surprising given that the electron doses needed for imaging far exceed those which destroy samples used in diffraction experiments. We discuss the conditions which make this possible and suggest that even with atomically thin, near-ideal sample configurations and microscopes properly designed to optimize the contrast to damage ratio, the 1.5 Angstrom resolution necessary for directly imaging the bases in DNA still requires electron irradiation doses that destroy much of the structure of the molecule. Preliminary experiments with heavy atom base labels like iodine suggest that the moderate increase in contrast with such tags may still be offset by vast increases in damage due to the production of reactive ions.