Polymer physics of intracellular phase transitions

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Intracellular organelles are either membrane-bound vesicles or membrane-less compartments that are made up of proteins and RNA. These organelles play key biological roles, by compartmentalizing the cell to enable spatiotemporal control of biological reactions. Recent studies suggest that membrane-less intracellular compartments are multicomponent viscous liquid droplets that form via phase separation. Proteins that have an intrinsic tendency for being conformationally heterogeneous seem to be the main drivers of liquid–liquid phase separation in the cell. These findings highlight the relevance of classical concepts from the physics of polymeric phase transitions for understanding the assembly of intracellular membrane-less compartments. However, applying these concepts is challenging, given the heteropolymeric nature of protein sequences, the complex intracellular environment, and non-equilibrium features intrinsic to cells. This provides new opportunities for adapting established theories and for the emergence of new physics. The internal structure of cells is organized into compartments, many of which lack a confining membrane and instead resemble viscous liquid droplets. Evidence is mounting that these compartments form via spontaneous phase transitions. The internal structure of cells is organized into compartments, many of which lack a confining membrane and instead resemble viscous liquid droplets. Evidence is mounting that these compartments form via spontaneous phase transitions.