Interplay between Basepairing and Electrostatic Interactions Determines the Phase Behaviors of DNA Nanostar and Polylysine Mixtures

Liquid-liquid phase separation (LLPS) is widely recognized as a key mechanism regulating various biological processes. However, how distinct driving forces for phase separation interact to determine phase behaviors remains unclear. In this study, we explore the interplay between basepairing and electrostatic interactions by investigating mixtures of DNA nanostars and polylysine, where the strengths of these interactions are expected to respond oppositely to changes in salt concentration. We develop a mean-field model that incorporates both types of interactions within a consistent framework and derive an approximate free energy using Classical Density Functional Theory (CDFT). Our theoretical predictions align with experimental observations, revealing diverse phase behaviors that are modulated by salt concentration and temperature. Our results indicate that basepairing and electrostatic interactions sometimes compete and, in some other cases, cooperate to stabilize the dense phase. These findings provide a quantitative understanding of the interplay between these interactions under biologically relevant conditions.