Life Sciences Faculties

Phase separation is generally a thermodynamic process in which a mixture reaches its lowest free energy state by self-assembling into meso- (or macro-) scale regions that are concentrated or dilute in a given molecular component. Familiar examples include the immiscibility of water and oil, the demixing of metal atoms in alloys, and the mesoscale formation of emulsions such as milk or paint. The fundamental physics behind both the equilibrium and non-equilibrium aspects of phase separation are well understood and this talk will begin with a brief review of those. A rapidly growing body of experiments suggests that phase separation is responsible for the formation of membraneless domains (also known as biomolecular condensates, with length scales on the order of microns) in biological cells. These compartments allow the cell to organize itself in space and can promote or inhibit biochemical reactions, provide regions in which macromolecular assemblies can form, or control the spatial organization of DNA (assembled with proteins as chromatin) in the cell nucleus. I will review some recent examples based on experiments done at the Weizmann Institute on phase separation of proteins and of chromatin in the nucleus and show how physics theory has led to their understanding. In the latter case, a new paradigm is emerging in which the genetic material is not necessarily uniformly distributed within the nucleus but separated into domains which in some cases, have a complex, “marshland”, mesoscale structure. But while many of the equilibrium aspects can be at least semi-quantitatively understood by extensions of statistical physics, biological systems often do not have constant overall compositions as is the case in the examples of oil-water, alloys and emulsions; for example, over time, the cell produces and degrades many proteins. The recent understanding of such strongly non-equilibrium effects has informed the theoretical physics of phase separation and has allowed us to establish a framework in which biological noise can be included.
* Collaborations: Omar Arana-Adame, Gaurav Bajpai, Dan Deviri, Amit Kumar (Dept. Chemical and Biological Physics), group of Emmanuel Levy (Dept. Structural Biology) and group of Talila Volk (Dept. Molecular Genetics)