Supercoiling Drives DNA-Protein Co-Condensation

Abstract

The co-condensation of DNA and proteins plays an important role in genome compaction, including heterochromatin formation and chromosome segregation. Meanwhile, transcription and replication continuously generate DNA supercoiling, yet how the resulting torsional stress affects co-condensation remains poorly understood. Here, by coupling DNA elasticity to a protein concentration field, we show that supercoiling acts as a topological catalyst for co-condensation through a mutually reinforcing interplay with protein wetting. Specifically, protein wetting facilitates twist-to-writhe conversion, generating highly writhed DNA conformations that in turn promote capillary collapse into a protein-rich droplet. In the absence of supercoiling, DNA remains kinetically trapped in metastable extended states within our model, whereas sufficiently strong supercoiling removes the nucleation barrier and enables spontaneous co-condensation. These results establish topology as a distinct control parameter for biomolecular condensation and provide a mechanical framework for how active genomic processes can dynamically regulate large-scale genome organization.