Molecular and environmental determinants of biomolecular condensate formation

Biomolecular condensate formation has been implicated in a host of biological processes and has found relevance in biology and disease. Understanding the physical principles and underlying characteristics of how these macromolecular assemblies form and are regulated has become a central focus of the field. In this Review, we introduce features of phase-separating biomolecules from a general physical viewpoint and highlight how molecular features, including affinity, valence and a competition between inter- and intramolecular contacts, affect phase separation. We then discuss sequence properties of proteins that serve to mediate intermolecular interactions. Finally, we review how the intracellular environment can affect structural and sequence determinants of proteins and modulate physical parameters of their phase transitions. The works reviewed highlight that a complex interplay exists between structure, sequence and environmental determinants in the formation of biomolecular condensates.

Automated summary

In this Review, the formation and regulation of biomolecular condensates are discussed. The physical principles and characteristics of phase-separating biomolecules are introduced, emphasizing the impact of molecular features on phase separation. The role of protein sequence properties in mediating intermolecular interactions is also explored. Additionally, the influence of the intracellular environment on protein structure and sequence determinants, as well as the modulation of physical parameters of phase transitions, is reviewed.