Effect of ethanol on the elasticities of double-stranded RNA and DNA revealed by magnetic tweezers and simulations.

This article investigates the effects of ethanol on the elastic properties of double-stranded RNA (dsRNA) and DNA (dsDNA) using high-precision magnetic tweezers (MT) experiments and all-atom molecular dynamics (MD) simulations. It reports that increasing ethanol concentration (up to 40% vol/vol) decreases the bending persistence lengths and contour lengths of both dsRNA and dsDNA, indicating a softening of their bending elasticity. Additionally, ethanol weakens the positive twist–stretch coupling of dsRNA—mediated by major groove widening—through enhanced ion binding that narrows and clamps the major groove, while it strengthens the negative twist–stretch coupling of dsDNA by promoting ion binding around phosphate groups and enhancing the helical radius-mediated deformation pathway. These effects are attributed primarily to ethanol's lowering of the solution dielectric constant, which enhances ion neutralization and alters electrostatic interactions around the nucleic acids. The findings provide insight into how low-polarity cosolvents like ethanol modulate nucleic acid mechanics, with implications for understanding nucleic acid behavior in crowded cellular environments and for the design of RNA/DNA-based nanomaterials.