Mechanics of Phase Separation in, on, and around the Genome*

In this talk I will discuss our work to understand and engineer intracellular phase transitions, which play an important role in organizing the contents of living cells. Membrane-less RNA and protein rich condensates are found throughout the cell, and regulate the flow of genetic information. This functional role is particularly important in the nucleus, where phase separated condensates form in, on, and around chromatin, a complex polymeric material which stores information and controls gene expression. However, the way in which chromatin impacts the dynamics of phase separation is poorly understood. We have recently demonstrated that droplet growth dynamics are directly inhibited by the chromatin-dense environment, which gives rise to an anomalously slow coarsening exponent, β≈0.12, contrasting with the classical prediction of β≈1/3. This arrested growth can arise due to subdiffusion of individual condensates, with a theoretical prediction of β=α/3, where α is the diffusive exponent, in good agreement with the measured subdiffusive exponent of α≈0.5. I will discuss the implications of these findings for genomic structure and function, and ongoing work to use condensates as probes of the viscoelastic environment within living cells.