Investigation on the Structural Variation of Self-Assembled Lipid Bicellar Mixtures Upon Environmental Stimuli and Addition of PEGylated Compounds

Bilayered mixed micelle, known as “bicelle”, has been extensively used as the biological membrane models in deciphering membrane-associated proteins. The bicellar mixtures normally constitute of long-chain and short-chain phospholipids in aqueous solutions. Disc-like morphology has been assumed for such mixtures where a bilayer fragment of long-chain phospholipids is sequestered by short-chain lipids at the rim. Recently, other structures such as vesicles, elongated micelles, and lamellae have also been found in bicelles as temperature, concentration, and salinity vary. The nano-sized bicellar discs (nanodiscs) and vesicles have great potential to be used as ingredient carriers for imaging and therapy. The research motivation is stimulated from enabling the nanodiscs and vesicles for future in vivo application. The objective of my research is to understand the interactions in the bicellar systems under effects of the doping negatively charged lipids, PEGylated lipids with different PEG molecular weights and molar ratios, and other types amphiphilic compounds on the morphological variation under different conditions. The first problem is that the stability of the size and shape of bicelles is hard to be achieved by the zwitterionic components. I significantly improved the stability of bicellar assemblies by doping the negatively charged long-chain lipids, in which way the interparticle electrostatic repulsions play an important role. Furthermore, Polyethylene glycol (PEG) surface-coated nanoparticles have been confirmed to be an effective approach to prolong their in vivo circulation time. I further investigated the interaction between bicelles with a reverse Pluronic triblock copolymer which constitutes of two hydrophobic ends (polypropylene glycol, PPG) and a PEG hydrophilic middle block (PPG-PEG-PPG). The triblock copolymer is capable of linking bicellar nanodiscs and facilitating the formation of various structures such as vesicles and stacking. The structural characterizations were mainly investigated via small angle neutron/X-ray scattering, dynamic light scattering, and transmission electron microscopy. The assembled structures were rationalized by scattering models such as flat cylinders, core- shell spheres, ellipsoids, and lamellae. My research outcomes allow interested researchers to further understand and utilize the bicelle templates for biomimetic and advanced material applications.