Surprises in the liquid-liquid phase separation of multivalent DNA complexes

The liquid-liquid phase separation of multivalent DNA complexes--often called DNA nanostars--follows the upper critical solution temperature (UCST) behavior. At temperatures below the binodal curve, DNA nanostars phase separate into a dense liquid-like phase and a dilute gas-like phase. Above the binodal curve, the interactions between nanostars are negligibly weak and the system enters a one-phase region. In this talk, I will describe a straightforward microfluidics-based approach for constructing the phase diagram of DNA nanostars. Using our approach, we quantify the equilibrium densities of both the liquid and gas phases as a function of temperature for different star architectures, thereby constructing the phase diagrams in the density-temperature plane. Surprisingly, we find that the phase behavior of DNA nanostars is much more complex than originally anticipated, which we rationalize using an associating fluid-based model. Our results could help shed light on the interplay between the self-assembly of biomolecular complexes and liquid-liquid phase separation in other material platforms, including proteins and other nucleic acids.