Unraveling DNA dynamics using atomic force microscopy

The elucidation of structure–function relationships of biological samples has become important issue in post‐genomic researches. In order to unveil the molecular mechanisms controlling gene regulations, it is essential to understand the interplay between fundamental DNA properties and the dynamics of the entire molecule. The wide range of applicability of atomic force microscopy (AFM) has allowed us to extract physicochemical properties of DNA and DNA–protein complexes, as well as to determine their topographical information. Here, we review how AFM techniques have been utilized to study DNA and DNA–protein complexes and what types of analyses have accelerated the understanding of the DNA dynamics. We begin by illustrating the application of AFM to investigate the fundamental feature of DNA molecules; topological transition of DNA, length dependent properties of DNA molecules, flexibility of double‐stranded DNA, and capability of the formation of non‐Watson–Crick base pairing. These properties of DNA are critical for the DNA folding and enzymatic reactions. The technical advancement in the time‐resolution of AFM and sample preparation methods enabled visual analysis of DNA–protein interactions at sub‐second time region. DNA tension‐dependent enzymatic reaction and DNA looping dynamics by restriction enzymes were examined at a nanoscale in physiological environments. Contribution of physical properties of DNA to dynamics of nucleosomes and transition of the higher‐order structure of reconstituted chromatin are also reviewed. WIREs Nanomed Nanobiotechnol 2011 3 574–588 DOI: 10.1002/wnan.150 This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology