Competition between self-assembly and phase separation governs high-temperature condensation of a DNA liquid

In many biopolymer solutions, attractive interactions that stabilize finite-sized clusters at low concentrations also promote phase separation at high concentrations. Here we study a model biopolymer system that exhibits the opposite behavior: Self-assembly of DNA oligonucleotides into finite-sized, stoichiometric clusters, known as "DNA nanostars", tends to inhibit phase separation of the oligonucleotides at high temperatures. We use microfluidics-based experiments to map the phase behavior of DNA nanostars at high concentrations of divalent cations, revealing a novel phase transition in which the oligonucleotides condense upon increasing temperature. We then show that a theoretical model of competition between self-assembly and phase separation quantitatively predicts changes in experimental phase diagrams arising from DNA sequence perturbations. Our results point to a general mechanism by which self-assembly shapes phase boundaries in complex biopolymer solutions.