The current understanding of DNA structure and its interactions with other molecules relies overwhelmingly on crystallographic and NMR structural studies. These techniques are typically limited to short DNA fragments on the order of 10 bases long, about a single turn of the helix. The extent to which DNA sequences thus resolved resemble similar sections of long biologically relevant DNA molecules in their native environment remains hard to predict.
Recent dramatic improvements in atomic force microscopy (AFM) have established it as the only technique with a demonstrated high-resolution imaging capability of long DNA molecules in a nearly native environment. Using frequency-modulation AFM we have been able to reveal deviations of constrained DNA molecules from canonical B-form, as well as the hydration structure of single DNA molecules. Here, I will review these findings and our contributions to AFM technology that have made them possible. | 
