BPS2026 – Molecular contact map of biomolecular condensates shows connectivity giving rise to mechanical properties

Phase separation of biomolecules is known to enable the temporary disruption of homogeneity within a cytosol, creating a space that is compositionally distinct from its exterior. Such subcellular compartmentalization is crucial to understanding life, especially considering that most life functions by defying entropy. Presumably for their reversibility and internal diffusivity, these sub-compartments are often liquids instead of being solid aggregates. In this aspect, we posed a question: what are the physical criteria that enable a liquid phase? To elaborate, it is generally accepted that multivalent and weak interactions are required, but how much force and valency exactly are operating to maintain a liquid subphase? Furthermore, at which point do they start to turn into gels and solids? How do interactions between molecules give rise to macro-scale mechanical properties? To address these questions, we employed a DNA-Nanostar model system and cryo-electron tomography to directly visualize the monomers connected to one another. With this “contact map” we assess how molecular factors give rise to bulk mechanical properties quantitatively. We focus on the threshold of the liquid-gel-solid transition and how storage and loss modulus can be explained in terms of molecular connectivity.