Cholesterol Distribution and Raft-Like Phase Behavior in Asymmetric Lipid Membranes

Cell membranes serve as dynamic interfaces that regulate the exchange of materials and signals between a cell and its environment, while also helping to maintain its structural integrity. In eukaryotic cells, membrane asymmetry–where the two leaflets have different lipid compositions or numbers—plays a critical role in organizing lipids, modulating phase behavior, and influencing cellular function. This thesis investigates how lipid organization and mechanical stresses, particularly differential stress and cholesterol distribution, shape the behavior of asymmetric membranes. Using coarse-grained molecular dynamics simulations and theoretical modeling, I analyze how lipid composition influences cholesterol partitioning and how stress differences in the membrane govern cholesterol equilibrium. Following this, the Cooke lipid model, which has been extensively characterized on the curvature-elastic front, is extended to also represent ternary mixing thermodynamics in order to study raft-like membrane domains. In particular, I capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. The elasticity and lipid diffusion for both phase-separated and pure systems, and how they change upon the addition of cholesterol, are also examined. In addition, a thermodynamic framework is developed to describe the interplay between membrane composition, lipid asymmetry, and differential stress, providing new insight into the fundamental physical principles governing membrane phase behavior. These results have broad implications for understanding cellular signaling, membrane protein function, and the mechanical properties of biomembranes.