Developments in describing equilibrium phase transitions of multivalent associative macromolecules

Biomolecular condensates are distinct cellular bodies that form and dissolve reversibly to organize cellular matter and biochemical reactions in space and time. Condensates are thought to form and dissolve under the influence of spontaneous and driven phase transitions of multivalent associative macromolecules. These include phase separation, which is defined by segregation of macromolecules from the solvent or from one another, and percolation or gelation, which is an inclusive networking transition driven by reversible associations among multivalent macromolecules. Considerable progress has been made to model sequence-specific phase transitions, especially for intrinsically disordered proteins. Here, we summarize the state-of-the-art of theories and computations aimed at understanding and modeling sequence-specific, thermodynamically controlled, coupled associative and segregative phase transitions of archetypal multivalent macromolecules.