DNA Supercoiling Facilitates Co-Condensation with Proteins

DNA supercoiling naturally arises during transcription and replication — as the polymerase advances along the double helix, it unwinds DNA upstream and overwinds it downstream, generating torsional stress that drives the formation of negative and positive supercoils, respectively. While DNA–protein co-condensation underlies key genome-organization processes such as nucleolar assembly, heterochromatin formation, and ParABS-mediated chromosome segregation, the role of DNA supercoiling in these processes remains largely unexplored. Here, we develop a model that couples the twist dynamics of DNA with a diffusive protein concentration field and study how supercoiling modulates DNA–protein co-condensation. Our simulations reveal that supercoiling promotes co-condensation through a mutually reinforcing coupling between DNA deformation and protein assembly: supercoiling facilitates the formation of protein-rich droplets, which in turn accommodate and stabilize DNA writhe. These results suggest that DNA supercoiling provides an additional thermodynamic pathway for DNA–protein co-condensation that complements direct binding interactions, potentially shaping genome organization across diverse biological contexts.