Designing the Morphology of Multiphase DNA Condensates

The physics and morphology of biomolecular condensates obtained from liquid-liquid phase separation underpin numerous biological processes. Biomolecular condensates can form complex multiphase morphologies, such as nested configurations 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 is dictated by surface tensions between pairs of phases, we develop coarse-grained molecular dynamics simulations to investigate how surface tension depends on the microscopic properties of DNA nanostars (size, valence, bending rigidity, Debye length, binding strength, types of sticky ends, etc.). The morphologies of condensates with two types of DNA nanostars have been systematically studied. We find that Janus-like morphologies are ubiquitous because the two dense phases have similar surface tensions. On the other hand, nested morphologies are rare as they require the two dense phases to have drastically different surface tensions, which is only possible for highly asymmetric types of DNA nanostars (different sizes, valences, and type distributions of sticky ends). Based on this principle, more elaborate morphologies can be designed via various methods such as adopting heterogeneous nanostars, introducing crosslinkers, increasing size disparities, etc., rendering DNA nanostars a promising material in bioengineering.