Abstract Droplet formation has emerged as an essential concept for the spatiotemporal organisation of biomolecules in cells. However, classical descriptions of droplet dynamics based on passive liquid-liquid phase separation cannot capture the complex situation inside cells. This review discusses three distinct aspects that are crucial in cells: (i) biomolecules are diverse and individually complex, implying that cellular droplets posses complex internal behaviour, e.g., in terms of their material properties; (ii) the cellular environment contains many solid-like structures that droplets can wet; (iii) cells are alive and use fuel to drive processes out of equilibrium. We illustrate how these principles control droplet nucleation, growth, position, and count to unveil possible regulatory mechanisms in biological cells and other applications of phase separation.
Zwicker et al. (2025) studied this question.