A Mesoscopic Model for the Condensation of Intrinsically Disordered Proteins

Proteins containing intrinsically disordered regions (IDRs) often mediate the formation of phase-separated biomolecular condensates involved in cellular signaling, epigenetic inheritance, and disease pathology. Mechanistically, these protein condensates are thought to be important for physical sequestration, membrane selectivity, and control of biochemical microenvironments. However, assessing the physical validity of these functions requires an understanding of both the detailed microstructure and particle hydrodynamics within these compartments. Here, we develop a method for generating multiscale coarse-grained models for the condensation of proteins containing both ordered and disordered regions. Using Langevin Dynamics simulations, we study how electrostatic and entropic forces combine to control time-dependent liquid, gel, and solid transitions. Furthermore, we probe the physical mechanisms for the reversibility of protein condensates under changes in temperature, pH, and ionic strength. From this physical framework, we ask if size exclusion plays a role in how protein condensates achieve selectivity. We leverage Voronoi diagrams to understand size-specific tracer migration within protein condensates which undergo gelation.