High-Resolution Atomic Force Microscopy Imaging of Nucleic Acids

Abstract

Exploring the limits of spatial resolution has been a constant in the history of atomic force microscopy imaging. Since its invention in 1986, the AFM has beaten the barrier of resolution continuously, thanks to technical developments, miniaturization of tips, and implementation of new imaging modes. The double helix structure of DNA has been always at the horizon of resolution. Today, this milestone has been reached, not only imaging DNA but also its close relative double-stranded RNA. Here, we provide a comprehensive description of the methods employed and the steps required to image the helical periodicity of these two nucleic acids with the sample immersed in a buffer solution.