Figure 5. Phase separation and connection to metabolism.

(A) A phase diagram for any biomolecule showing various transitions of its state; a state of liquid–liquid phase separation can be achieved, theoretically for any biomolecule. However, the boundaries of transitions are different for each biomolecule. (B) Advantages of phase-separated biomolecules: their unique biophysical properties may regulate mesh size and chemical properties of the condensate, which enables condensates to serve as molecular filters, restricting the diffusion of molecules through their boundaries based on, e.g. their sizes. Phase-separated membraneless organelles can also act as storage deposits, for example of inactive enzymes that would otherwise be waste material (e.g. glyconeogenesis and glycolytic enzymes could in principle phase separate in such granules when one or another competing metabolic pathway is utilized). At the edge of the biological condensate, due to the viscosity and the surface tension of the liquid phase of the condensate, force is generated. Such force could in principle, be utilized by various pathways that might require additional energy to complete. Condensates also function as organizing centers for polymerization, as shown for example, for actin filaments or the microtubule-organizing centers; however, it is yet unknown if enzymatic filaments follow an analogous principle. Signal amplification is also an attractive idea, where for example, inactive metabolic pathways become active after phase-separated signaling molecules, which may reach critical concentrations to regulate the ‘firing’ of the enzymatic pathway. Metabolons may organize on membranes via liquid–liquid demixing and phase-separation processes, having an affinity toward the boundaries of membranes (see also text). (C) Illustration of the usual phosphorylation patterns of proteins in phase-separated membraneless organelles which have effect on phase transitions, e.g. by decreasing or increasing biomolecular binding affinity. (D) Regulators/effectors of phase transitions.