(672f) Probing Phase Transitions in Dynamic Biopolymer Complexation

In nature, biopolymers partition into dynamic compartments to facilitate and regulate their interactions. These dynamic compartments are referred to as membraneless organelles (e.g., nucleolus, P bodies, stress and germ granules) and consist of biopolymer-rich interiors that rapidly assemble and disassemble to form liquid droplets, hydrogels or fibril structures. However, the physical interactions that affect the formation, dissolution, and regulation of these assemblages are poorly understood, yet vital in determining their function in normal and disease states. Therefore, there is a strong need to investigate the underlying mechanisms that drive dynamic biopolymer complexation and develop an understanding of their biochemical function. Interestingly, polyelectrolyte complexes produced in vitro using simple homopolymers are strikingly similar to the membraneless organelles found in vivo. Polyelectrolyte complexation is an entropically driven process, where electrostatic attraction between oppositely charged polymers results in a release of bound counter-ions and rearrangement of water molecules. Under defined conditions, oppositely charged polyelectrolytes can form complexes consisting of a dense polymer-rich phase (liquid coacervate or solid precipitate) in a polymer-depleted aqueous phase. Whether complexation results in a liquid or solid precipitate depends on the strength of electrostatic interactions, which are mediated by salt concentration, acidity/basicity of the monomers and their distribution along the polymer backbone. In this work, we investigate the forces that govern membraneless organelle formation by engineering model polypeptide analogs and systematically studying their phase transition behavior. From a broad perspective, our work holds the potential to develop a basic understanding of protein/polyelectrolyte complexation, impacting design of novel functional biomimetic materials.