Lihiniya Kumarage, Teshani Omanthika2024-08-162024-08-162024-08-15vt_gsexam:41250https://hdl.handle.net/10919/120939The lipid bilayer, the fundamental structure of cell membranes, exemplifies a highly adaptable molecular assembly with characteristics that have been fine-tuned through evolution to meet the diverse functional needs of cells. These bilayers must strike a delicate balance: they need to be sufficiently rigid to act as protective barriers, yet fluid enough to facilitate the diffusion of proteins and molecular clusters crucial for various biological processes. Owing to their multifunctional nature, lipid membranes are not only vital in biological contexts but also in numerous practical applications, such as artificial cells, drug-delivery nanocarriers, and biosensors. Both biological and synthetic lipid membranes frequently incorporate molecular or nanoscale additives that modify their properties through a range of mechanisms. Gaining a comprehensive understanding of how lipid membranes interact with these additives is an area of active research, particularly with the advent of advanced high-resolution characterization techniques that reveal both the static and dynamic behaviors of these systems. This dissertation investigates the impact of small molecular additives – specifically natural and synthetic sterols – on the structure, elasticity, and organization of biomimetic lipid membranes. Utilizing advanced scattering techniques and other methods, the research elucidates the intricate interplay between the membrane composition, structure, and elasticity. Key findings demonstrate that, unlike previous observations, cholesterol significantly affects the bending rigidity of lipid membranes regardless of chain unsaturation, when measured on mesoscopic length and time scales. Interestingly, the replacement of cholesterol with engineered molecules, comprised of a sterol unit that is chemically conjugated to one or both of the lipid chains, results in further enhancement in the membrane bending rigidity and mechanical stability, making them a promising additive for advanced liposomal drug delivery systems. Further studies on phase-separating membranes illustrate the effective use of sterol-modified lipids in regulating the formation and size of distinct lipid domains implicated in protein recruitment and biological function. This work advances the current understanding of membrane biophysics and paves the way for novel therapeutic strategies and biomaterial designs.ETDenIn Copyrightliposomal and supported membranesstructural propertiesmembrane dynamicsarea per lipidbending rigidityDissertation