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

TL;DR

This study reveals how the competition between self-assembly into DNA nanostars and phase separation influences high-temperature condensation in biopolymer solutions, combining experiments and modeling.

Contribution

It introduces a theoretical model that predicts phase behavior changes due to DNA sequence variations, highlighting the role of self-assembly in phase boundary regulation.

Findings

DNA nanostars inhibit phase separation at high temperatures

A phase transition where DNA condenses upon heating was observed

Model accurately predicts effects of sequence perturbations on phase diagrams

Abstract

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.