Images of single-stranded nucleic acids by scanning tunnelling microscopy

The scanning tunnelling microscope has the potential to resolve the structure of biological molecules with atomic detail. Progress has been made in the imaging of dried, unshadowed double helices of DNA4-7 and in recording images of DNA under water. Also, images of unshadowed complexes of DNA with the RecA protein from Escherichia coli indicate that this technique may not be restricted to thin biological samples. Here we present images of polydeoxyadenylate molecules aligned in parallel, with their bases lying flat on a surface of highly oriented pyrolytic graphite and with their charged phosphodiester backbones protruding upwards. Based on these images, a molecular model has been built which suggests the presence of a hydrogen bond that could stabilize the parallel alignment. Our micrographs demonstrate the potential application of scanning tunnelling microscopy in structural studies of nucleic acids and provide evidence that it could be used to sequence DNA.