Phase separation across membranes and condensates in cell organization and function

Abstract

Phase separation is a fundamental principle of cellular organization that typically leads to two coexisting phases: a dense one, where intermolecular interactions are stronger and molecules are more tightly packed, and a dilute, less packed phase, with weaker interactions and lower molecular concentration. This process drives the formation of both lateral membrane domains (rafts) and liquid-like protein and nucleic acid condensates. This Review explores the dynamic interplay between biomolecular condensates and membrane lipid domains and how phase separation occurs in the three-dimensional (bulk) cellular interior and at two-dimensional membrane interfaces. We examine how membranes act as platforms influencing condensate formation and function and, conversely, how condensates modulate membrane properties and organization. By highlighting diverse examples from cell signalling, tight-junction assembly and stress responses, we emphasize how these coupled interactions are crucial for cellular organization, function and fitness.