Liquid-Liquid Phase Separation of Biological Systems

Biomolecular condensates are two- and three-dimensional cellular compartments that concentrate specific collections of proteins, nucleic acids and small molecules without an encapsulating membrane. Many condensates behave as dynamic liquids, and are believed to form through liquid-liquid phase separation (LLPS) driven by interactions between multivalent macromolecules. The biochemical and cellular functions of condensates arise from composition—the specific exclusion or enrichment of molecules. While much is known about the factors that dictate the macromolecular composition of condensates, our understanding of small molecule composition remains limited. In my talk I will describe our recent experimental and computational studies of the partitioning of small organic compounds into condensates. These have revealed a generic hydrophobicity that emerges in condensates upon LLPS, which then governs the enrichment and exclusion of organic compounds based on their physical properties. Additionally, I will discuss a new direction in my lab focused on understanding how chromatin may be organized by LLPS, and dynamically regulated by various remodeling machineries. These behaviors may contribute to formation of functionally distinct compartments in the eukaryotic nucleus, which are important to processes including gene regulation and DNA repair.