Ethanol-induced Condensation and Decondensation in DNA-Linked Nanoparticles—A Nucleosome-Like Model for the Condensed State

Inspired by the conventional EtOH precipitation strategy, ethanol condensation has been applied as a routine method to dynamically tune “bond” lengths (i.e., the distances between adjacent nanoparticles that are linked by DNA) and the thermal stabilities of colloidal crystals engineered with DNA. However, the underlying mechanism of how the DNA bond changes in this class of colloidal crystals in response to ethanol remains unclear. Here, we conducted a series of all-atom molecular dynamic (MD) simulations to explore the free energy landscape toward DNA condensation and decondensation. Our simulations confirm that DNA condensation is energetically much more favorable under 80% ethanol conditions than in pure water, as a result of ethanol’s role in enhancing electrostatic interactions between charged species. Moreover, the condensed DNA adopts B-form in pure water and A-form in 80% ethanol, which indicates the higher-order transition does not affect DNA’s conformational preferences. We further propose a nucleosome-like supercoiled model for the DNA condensed state, and we showed that the DNA end-to-end distance matches the experimentally measured DNA bond length of about 3 nm in the fully condensed state for DNA where the measured length is 16 nm in water. Overall, this study provides an atomistic understanding of the mechanism underlying ethanol-induced condensation and water-induced decondensation, whereas our proposed nucleosome-like model allows the design of new strategies for interpreting experimental studies of DNA condensation.