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.

生物分子凝聚物的形成与许多生物过程有关，并已发现与生物学和疾病的相关性。了解这些大分子组装体如何形成和调节的物理原理和基本特征已成为该领域的中心焦点。在这篇综述中，我们从一般物理角度介绍了相分离生物分子的特征，并强调了分子特征（包括亲和力、化合价以及分子间和分子内接触之间的竞争）如何影响相分离。然后我们讨论用于介导分子间相互作用的蛋白质的序列特性。最后，我们回顾了细胞内环境如何影响蛋白质的结构和序列决定因素并调节其相变的物理参数。