Figure 1.

Liquid–liquid phase separation (LLPS) of macromolecules. (A) During LLPS, a homogenous solution of macromolecules is separated into dense liquid droplets and a diluted phase. Liquid droplets are dynamic and exchange their components with the diluted phase (IDP, intrinsically disordered protein; IDF, intrinsically disordered fragment). (B) Multivalent interactions in liquid droplets include electrostatic, cation–π and π–π interactions. (C) Smaller droplets may fuse into larger condensates. Upon prolonged stress, the liquid condensates may be irreversibly transformed into aberrant solid aggregates with amorphous and/or amyloid structures. During the transition from liquid to solid state, additional droplets, oligomers or small aggregates can be incorporated into larger aggregates.