Executive Summary : | Liquid-liquid phase-separation (LLPS) is a process that occurs in the crystallization of globular proteins, aqueous polymer mixtures, polymer-colloid mixtures, and food grade protein-polyelectrolyte mixtures. It is often discussed as the mechanism for the formation of membrane-less bodies known as biocondensates in the cytoplasm and nucleus of cells. These bodies contain soluble misfolded or intrinsically disordered proteins with oppositely charged biopolymers. The formation, structure, dynamics, and their mutual interplay are important topics in the physics of soft matter. This project aims to study LLPS of model intrinsically disordered proteins (IDPs) using rheological tools and computer simulations. The models chosen are amyloid-beta and gliadin IDPs, which are associated with neurodegenerative diseases like Alzheimers and Parkinsons. The experimental component will focus on studying the phase behavior of the model IDPs, rheological properties of the phase-separated domains, and the time evolution of the rheological response to understand the dynamics of phase-separation. The computer simulation component will build a coarse-grained model for IDPs and additives, predict equilibrium liquid-liquid phase boundaries, and study the dynamics along quenching routes. The project aims to understand the structure and dynamics of LLPS in IDPs, which has relevance not only to coacervates used in food, cosmetic, and pharmaceutical formulations but also to the formation of biocondensates in plant and animal cells. The goal is to link these studies with molecular biology of the biocondensates to gain a complete understanding of the structure-dynamics-function relationship. |