Hydrophilicity of a Single DNA Molecule

Water hydration is ubiquitous to biological molecules and surfaces at the nanoscale and critical to the mediation of all biological processes. Still, the wetting of biological surfaces, such as proteins and DNA, is not completely understood due to a lack of methods with sufficient resolution and/or sensitivity under bioactive conditions or moisturized environments. Moreover, a fundamental understanding of hydrophobic nonspecific interactions is still emerging. Here, we describe the mechanisms leading to height formation in ambient atomic force microscopy AFM and use them to show how the apparent height of DNA molecules is affected by their local hydrophilicity/hydrophobicity relative to the supporting surface. In the case of mica, a common substrate for imaging DNA, water films with heights of up to 2 nm form on its surface in ambient conditions. These films might partially cover dsDNA molecules and lead to apparent molecular height loss. Nevertheless, such decrease in molecular height is not solely affected by substrate and surface hydration but by limitations in AFM height measurements of nanoscale structures and the chemistry of the surface, the tip, and the molecule. Our study on apparent height measurements is consistent with partial hydration of the molecule relative to the supporting surface. Our approach to nanoscale water affinity mapping could impact the study of biological processes where the role of water films and fluidity is relevant such as protein folding and protein DNA interactions.