Designing the Morphology of Phase-Separated DNA Condensates

The physics and morphology of biomolecular condensates that form via liquid-liquid phase separation underpin numerous biological processes. Biomolecular condensates can also form complex multiphase morphologies, such as the nested configuration of nucleoli that facilitate the production of ribosomes. Here, we investigate how to design the morphology of multiphase condensates that form in solutions of DNA nanostars. Since the morphology of multiphase condensates is dictated by surface energies between pairs of phases, we developed coarse-grained molecular dynamics simulations to investigate how surface energies depend on the properties of nanostars (size, number of arms, sequences of sticky ends on each arm), temperature, and electrostatic screening. We also systematically studied morphologies of condensates with two types of DNA nanostars. We found that Janus-like morphologies are ubiquitous because the two condensed phases have similar surface energies. On the other hand, nested morphologies are rare because they require the two condensed phases to have drastically different surface energies, which is only possible for highly asymmetric types of DNA nanostars (different numbers of arms, sizes, and distribution of sticky ends).