A Study of Phospholipid Vesicles: Investigating the Effect of Ionic Strength and New Synthetic Route Towards Deuterated Lipids

This dissertation focuses on two main projects: investigating the effect of monovalent salts on phospholipid vesicles and developing a new synthetic route towards deuterated lipids for further study. Inspired by the design to explore in depth the effect of ions on membrane, chapter one details the importance of oleic acid and its corresponding lipids, including various methods used to characterize the lipid bilayers. This chapter also describes the previously known effect of ions on lipid bilayers, as well as the benefit of deuterated lipids for many studies of membrane biology, biochemistry and biophysics using methods which are sensitive to proton deuterium isotopic labeling. Chapter two focuses on the effect of different monovalent salts on phospholipid vesicles. Our study demonstrates how a seemingly simple and often overlooked parameters such as salt or ion concentrations can be used to transform unilamellar to multilamellar vesicles while controlling the overall size of the vesicle and water core simultaneously even at sub physiological concentrations. We examine multiple transitioning stages of the neutral phospholipid vesicles with abrupt phase transitions at different concentrations which can be utilized as indicators for the formation of multilamellar vesicles and higher ordered hybrid structures for different lipids in different salt environment window. These observations help us further our understanding of cell signaling, translocation, intracellular biological functioning and cell division in different environments Chapter three focuses on our work on deuterated lipids. We developed a simple and mild approach to synthesize [D62] 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). This involves simple but high yielding reactions, starting with the hydrothermal metal catalyzed H/D exchange reactions of azelaic and nonanoic acids, then conjugating the two saturated alkyl chains in a cis-configuration, and finally assembling the deuterated tails to the phosphocholine headgroup via Steglich esterification. The deuteration percentage of each precursor, as well as the overall deuteration percentage of the final product is also discussed. Deuterated DOPC liposomes was characterized by dynamic light scattering, and the hydrodynamic radius was consistent and agreed well with its protonated analogue