Lipid membranes and the biophysics of protein-lipid interactions

Abstract

Lipid membranes are a fundamental structure of cells. In addition to compartmentalizing biological components and forming a physical barrier to protect against unwanted interactions. Membranes are a platform for protein signaling. This thesis investigates mechanisms of protein-lipid interactions based on the membrane's biophysical properties. First, we examine relationships between phase-separable membranes and 3D protein condensates, and we describe how thermodynamically coupling these systems can alter the details of their phase separation. We summarize key challenges in obtaining quantitative measurements of these coupled systems, and we present solutions to circumvent some of these challenges. Second, we use lipidomics to discover how common methods of making vesicles alter lipid compositions (or not) with respect to a stock solution. Third, we investigate the mechanisms of an enzyme in cholesterol synthesis, squalene monooxygenase. Specifically, we develop an approach to measure the effects of cholesterol levels and membrane curvature on the interaction of squalene monooxygenase's degron with the membrane surface. Fourth, we develop a template for implementing Wikipedia edits with undergraduates to increase students' appreciation and understanding of biophysics and biophysicists.