Heterogeneity of Molecular Crowding and Liquid-Liquid Phase Separation

The inside of a living cell is highly crowded with extremely diverse biomacromolecules, small metabolites and osmolytes. The molecular conditions in cells change dynamically and rapidly depending on the cell cycle and state, organelle, and compartment. Much remains unknown regarding how biomolecular interactions and reactions can proceed in a spatiotemporally specific manner in such crowded, heterogeneous, and dynamic molecular environments. Selective condensation/droplet formation of biomolecules via liquid-liquid phase separation may be critical for interactions and reactions inside cells. In this chapter, we briefly describe the heterogeneity of molecular environments inside cells and the biological roles of liquid-liquid phase separation that allows biomolecular interactions and reactions in such heterogenous molecular environments. Finally, we discuss the mutual relationship between molecular crowding and liquid-liquid phase separation.