Counterintuitive DNA destabilization by monovalent salt at high concentrations due to overcharging

Area of Science:

• Biophysics
• Chemical Physics
• Materials Science

Background:

• Monovalent salts are traditionally thought to stabilize nucleic acid duplexes by reducing electrostatic repulsion.
• This stabilization is attributed to weakening inter-strand charge repulsion.

Purpose of the Study:

• To investigate the effect of high concentrations of monovalent salts on DNA, RNA, and RNA-DNA duplex stability.
• To challenge the established understanding of salt effects on nucleic acid structures.

Main Methods:

• Force-induced hairpin unzipping experiments.
• Thermal melting experiments.
• All-atom and coarse-grained molecular simulations.

Main Results:

• Monovalent salts (LiCl, NaCl, KCl, RbCl, CsCl) at concentrations >1 M unexpectedly destabilize DNA, RNA, and RNA-DNA duplexes.
• High salt concentrations (1-4 M) decrease DNA duplex stability by ~0.3 k_BT/bp and melting temperature by ~10°C.
• All-atom simulations revealed overcharging, where excessive ion absorption inverts the net charge of the duplex.

Conclusions:

• High concentrations of monovalent salts can destabilize nucleic acid duplexes through overcharging, contrary to traditional beliefs.
• Overcharging is not limited to multivalent ions, impacting polyelectrolyte theory.
• Findings have significant implications for DNA nanomaterials, nanotechnology, and biophysics.