Abstract
In this thesis, we investigated the structure of mixing cationic lipid with anionic lipid. The cationic lipid and anionic lipid could form lipid pair through electrostatic interaction. We investigated the DOTAP/DPPG and the and DC-Cholesterol/DPPG systems at cationic to anionic lipid ratio of 0, 0.2, 0.4, 0.5, 0.6, 0.8, and 1. In the monolayer experiments, the pressure-surface area isotherm of the mixed lipid monolayer were measured with a Langmuir-Blodgett (LB) trough. We also prepared LB monolayer films on silicon substrates for AFM and X-ray reflectivity measurements. From the measured surface excess area of the mixed DOTAP/DPPG monolayer indicates that the interaction between the molecules is associative and the association effect reaches a maximum at around 40% DOTAP. As for the DC-Cholesterol/ DPPG system, the excess area data shows that the interaction is repulsive with peak values at 20%, then 60% of DC-cholesterol. The solution structures of the mixed system are characterized by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS). For the 1:1 cationic to anionic lipid ratio, both systems tend to form precipitates. For other ratios, unilamellar vesicles with diameters around 100 to 200 nm are formed. The vesicle size is larger for ratios near 1:1, such as the 40% and 60%. It is due to that cationic-anionic lipid pair tend to have lower spontaneous curvature and favors the formation of larger vesicles. Adding 30% short-chain lipid, the 1,2-Diheptanoyl-sn-glycero-3-phosphocholine (diC7PC), could disperse the DOTAP/DPPG vesicles into a coexistence phase of bicelles and vesicles, except the 1:1 ratio case. As for the DC-Cholesterol/DPPG system, adding diC7PC could not disperse the vesicles into bicelles. The bonding between the DC-Cholesterol and DPPG must be stronger than the DOTAP/DPPG system. By adding 30%DPPC for the 20% DOTAP/20% DPPG/30% diC7PC system, it is possible to prevent the precipitation of the 1:1 cationic/anionic lipid mixture and to induce the formation of bicelles and vesicles in coexistence. However, this does not work for the 20% DC-Cholesterol/20% DPPG/30% diC7PC system. It is found the complexation with DNA can occur for the cases when the ratio of cationic lipid to anionic lipid is larger than 1.