Bis(monoacylglycero)phosphate (BMP) is a negatively charged phospholipid found in elevated concentrations in the late endosome. BMP has an unusual structure and stereochemistry that are thought to be responsible for important roles in the endosome, including structural integrity, endosome maturation, and lipid/protein sorting and trafficking. The main objective of the work reported in this dissertation was to characterize the morphology and size distribution of BMP model membranes as a function of pH, ionic strength, concentration and lipid composition, using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Dynamic light scattering is a simple, non-invasive particle sizing technique that measures the hydrodynamic diameter of particles or macromolecules suspended in solution based on their interaction with light, whereas TEM provides valuable information on the morphology and sizes of particles.

Results presented in this dissertation demonstrate that BMP forms small, stable, lamellar vesicle structures, and that BMP induces the formation of small vesicles when mixed with typical phosphatidylcholine (POPC) membranes at specific concentrations. Morphological and size distribution studies on the interaction between BMP and ganglioside GM1 reveal that GM1 mixes with BMP at specific concentrations to form small (∼100 nm) spherical shaped vesicles with a narrow size distribution. This specific mixture of GM1 with BMP may be important for in vivo vesicular trafficking and lipid sorting in the endosome/lysosome pathways.

Finally, when ganglioside GM1, cholesterol (CHOL) and BMP lipids are incorporated in typical POPC dispersions at specific concentrations, they form vesicles with different morphology and size distributions. Taken together, results from these investigations give a further understanding to the role that BMP, GM1 and cholesterol may play in the late endosome, and allow for possible future studies in using BMP vesicles for drug delivery applications.