Supercoils Stabilize a "DNA Corset" Condensate with Torsion-Dependent Hysteretic Compaction.

Biomolecular condensates formed through phase separation are critical physical mechanisms for organizing membraneless compartments in eukaryotic cells. To achieve precise spatiotemporal control of biochemical reactions, cells must effectively regulate condensate size. The microscopic mechanism underlying these regulation processes, on the other hand, remains largely elusive. We herein explicitly incorporate DNA torsional flexibility into a coarse-grained DNA-protein "Bridging-Induced Phase Separation" model, enabling the direct simulation and visualization of how DNA supercoiling regulates the condensate structure and size. DNA supercoiling generates a compact "DNA corset" condensate with a dense DNA-protein core encircled by plectonemic loops that laminate the surface. Increasing supercoiling compacts the condensate, whereas torsional relaxation restores its size through entropy-driven expansion. For short DNA, this transition is fully reversible, whereas longer chains exhibit hysteresis in which compaction and relaxation follow distinct pathways and thresholds. Supercoiling, therefore, functions as a topological switch that couples twist-to-writhe conversion with condensate mechanics. These findings link DNA supercoiling to the dynamic control of chromatin condensates and provide a physical framework for the topology-based condensate design.