Charge Neutralization Drives the Shape Reconfiguration of DNA Nanotubes

• Published in: Angewandte Chemie International Edition 2018-05, Vol.57 (19), p.5418-5422
• Main Authors: Liu, Pi, Zhao, Yan, Liu, Xiaoguo, Sun, Jixue, Xu, Dede, Li, Yang, Li, Qian, Wang, Lihua, Yang, Sichun, Fan, Chunhai, Lin, Jianping
• Format: Article
• Language: English
• Subjects: Biomedical materials; Biomimetics; Channel gating; Channels; Chemical modification; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA nanotechnology; Electrostatic properties; Fluorescence Resonance Energy Transfer; Hydrophobicity; Magnesium; Membrane proteins; molecular channels; molecular dynamics; Molecular Dynamics Simulation; Nanotechnology; Nanotubes; Nanotubes - chemistry; Neutralization; Protein transport; Reconfiguration; SAXS; Scattering, Small Angle; Shape control; shape reconfiguration; Small angle X ray scattering; Structure-function relationships; Switches; X-Ray Diffraction
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201801498

Reconfiguration of membrane protein channels for gated transport is highly regulated under physiological conditions. However, a mechanistic understanding of such channels remains challenging owing to the difficulty in probing subtle gating‐associated structural changes. Herein, we show that charge neutralization can drive the shape reconfiguration of a biomimetic 6‐helix bundle DNA nanotube (6HB). Specifically, 6HB adopts a compact state when its charge is neutralized by Mg2+; whereas Na+ switches it to the expanded state, as revealed by MD simulations, small‐angle X‐ray scattering (SAXS), and FRET characterization. Furthermore, partial neutralization of the DNA backbone charges by chemical modification renders 6HB compact and insensitive to ions, suggesting an interplay between electrostatic and hydrophobic forces in the channels. This system provides a platform for understanding the structure–function relationship of biological channels and designing rules for the shape control of DNA nanostructures in biomedical applications. Tune the caliber: An electrostatic repulsive force yields DNA nanotubes in an expanded state in low‐counterion‐concentration environments. This force can be weakened by increasing the counterion concentration or be removed by using electroneutral ethyl‐phosphorothioate DNA. The shape of the DNA nanotubes can be controlled by manipulating the strength of the electrostatic repulsive force.