Hue Sun Chan
Departments of Biochemistry and Molecular Genetics,
University of Toronto, Toronto, Ontario M5S 1A8
Compartmentalization is essential for the physico-chemical processes that underlie biological function---especially in multi-cellular organisms---and was arguably one of the critical steps in the prebiotic evolution of a proto-cell that led to the many life forms on Earth today. The cell itself is a compartment demarcated by a lipid membrane, so are certain organelles ("little organs") such as the mitochondria and nuclei in our cells. There are, however, highly dynamic cellular compartments that are not bound by membranes. Examples include stress granules, germ granules, and the nucleolus. These bodies behave like mesoscopic liquid droplets, and are referred to as "membraneless organelles", or "biomolecular condensates" in general. It has been discovered recently that they are often underpinned by reversible liquid-liquid phase separation of intrinsically disordered proteins (IDPs) and nucleic acids; and they stimulate and regulate biological functions by creating their own environments. The formation/dissolution of biomolecular condensates is governed by the genetic information embodied in the chain sequences of nucleic acids and proteins. To gain physical insights into these fascinating novel phenomena, we developed analytical theories for sequence-specific IDP phase separations. Utilizing the random phase approximation and Flory-Huggins model from polymer physics, our theory provides a physical rationalization of experimental trends and points to a "fuzzy" mode of molecular recognition by charge pattern matching that likely bears on whether different IDP species remain miscible or demix when they phase separate.