Compartmentalization is essential for life and biology as we know it. While many compartments within a living cell are bound by a lipid membrane, there are also many compartments which lack membranes and instead form through biomolecular phase separation. This process involves the association or segregation of specific biomolecules into distinct regions known as condensates, which have unique molecular compositions compared to their surroundings. It is often driven by liquid-liquid phase separation (LLPS) and the liquid-like compartments are stabilized by many diverse noncovalent interactions including many nonspecific and dynamically rearranging contacts. Despite its importance to biological function and disease pathology, fundamental questions remain about how molecular properties govern condensate composition. For instance: How do different biomolecules interact within condensates? How do interaction strength, molecular shape, size, and solubility influence partitioning into or exclusion from these compartments?
Our lab aims to uncover the physical principles underlying these processes by studying disordered proteins using chemical theory and multiscale simulations. Utilizing coarse-knowledge of sequence-based parameters, we have developed methods to design protein sequences with desirable properties and phase separation propensity. We also have explored how globular proteins and other large cargo molecules partition into condensates based on their size and solubility. We also explore impacts of protein interactions on adhesion and disease pathology using molecular simulation methods. I will present our recent findings that shed light on these mechanisms and discuss their implications for understanding the physical basis of biological compartmentalization, adhesion and disease pathology.
