Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties

The cytoplasm is an aqueous, highly crowded solution of active macromolecules. Its properties influence the behavior of proteins, including their folding, motion, and interactions. In particular, proteins in the cytoplasm can interact to form phase‐separated assemblies, so‐called biomolecular condensates. The interplay between cytoplasmic properties and protein condensation is critical in a number of functional contexts and is the subject of this review. The authors first describe how cytoplasmic properties can affect protein behavior, in particular condensate formation, and then describe the functional implications of this interplay in three cellular contexts, which exemplify how protein self‐organization can be adapted to support certain physiological phenotypes. The authors then describe the formation of RNA‐protein condensates in highly polarized cells such as neurons, where condensates play a critical role in the regulation of local protein synthesis, and describe how different stressors trigger extensive reorganization of the cytoplasm, both through signaling pathways and through direct stress‐induced changes in cytoplasmic properties. Finally, the authors describe changes in protein behavior and cytoplasmic properties that may occur in extremophiles, in particular organisms that have adapted to inhabit environments of extreme temperature, and discuss the implications and functional importance of these changes. The properties of the cytoplasm affect protein self‐organization, including by regulating biomolecular condensation. The interplay between these is important in specialized functional contexts, including the establishment of cellular asymmetry and stress responses. In organisms that experience extreme conditions, adaptations to cytoplasmic properties are likely required to maintain this interplay.