Cellular Condensate Self-Organization: New Experiments and Theoretical Perspectives

Phase separation is generally a thermodynamic process in which a mixture of interacting molecules reaches its lowest free energy state by self-assembling into meso- (or macro-) scale regions that are concentrated in a given molecular component, which coexist with a dilute phase. A rapidly growing body of experiments suggests that phase separation is responsible for the formation of observed, micron-scale, biomolecular condensates which have important functions in biological cells.  I will review recent observations of phase separation of chromatin in the nucleus and show that a new paradigm is emerging in which the genetic material is not necessarily uniformly distributed within the nucleus, but phase separated into domains, generally near the nuclear periphery.   Intrinsically disordered proteins are another polymer-like system showing condensate formation with finite size. There too, experiments have motivated a conceptual paradigm shift, since such proteins can have several different conformations (under the same conditions) which can stabilize large protein clusters in aqueous solution whose interfacial tensions are ultra-low (relative to water-air tensions). 

* Based on collaborations with: Talila Volk, Dana Lorber, Amit Kumar (WIS), Gonen Golani (Haifa), Daniella Goldfarb and Manas Seal  (WIS), Tony Hyman, Mrityunjoy Kar, Omar Adame-Arana (MPI, Dresden), Gaurav Bajpai (Northeastern)