Opto-Electrostatic Determination of Nucleic Acid Double-Helix Dimensions and the Structure of the Molecule-Solvent Interface

A DNA molecule is highly electrically charged in solution. The electrical potential at the molecular surface is known to vary strongly with the local geometry of the double helix and plays a pivotal role in DNA-protein interactions. Further out from the molecular surface, the electrical field propagating into the surrounding electrolyte bears fingerprints of the three-dimensional arrangement of the charged atoms in the molecule. However, precise extraction of the structural information encoded in the electrostatic "far field " has remained experimentally challenging. Here, we report an optical microscopy-based approach that detects the field distribution surrounding a charged molecule in solution, revealing geometric features such as the radius and the average rise per basepair of the double helix with up to sub-Angstrom precision, comparable with traditional molecular structure determination techniques like X-ray crystallography and nuclear magnetic resonance. Moreover, measurement of the helical radius furnishes an unprecedented view of both hydration and the arrangement of cations at the molecule-solvent interface. We demonstrate that a probe in the electrostatic far field delivers structural and chemical information on macromolecules, opening up a new dimension in the study of charged molecules and interfaces in solution.