本論文主要研究帶正電荷的DOTAP和DC-Cholesterol與帶負電荷的DPPG之間以特定的分率(0、0.2、0.4、0.5、0.6、0.8、1)下所組成的分子單層膜及雙層膜結構，以及在水溶液之混合正電荷及負電荷樣品中加入短鏈1,2-Diheptanoyl-sn-glycero-3-phosphocholine (diC7PC)，以了解是否可形成平板微胞(bilayer micelle)，並另加入雙電性之DPPC，以協助其更易被diC7PC分散形成平板微胞。由正電荷及負電荷脂質分子構成的分子膜可具有較高的結構穩定性，分子膜的天然曲率也可由正電荷及負電荷脂質分子的比率作調控。實驗分為單層脂質分子膜實驗及雙層脂膜實驗兩部份，在單層脂質分子膜的實驗中，利用蘭牟爾-布羅吉槽來繪製表面壓-單分子佔據面積等溫曲線與在矽基板上製造單層脂膜，用於X光反射率的薄膜厚度及粗糙度量測，以及原子力顯微鏡的粗糙度量測與相位分析；在雙層脂膜實驗中，利用X光小角度散射來量測結構體在水溶液中形成的結構，並利用動態光散射儀量測粒徑及用穿透式電子顯微鏡觀察聚集結構的形貌。在單層脂膜的實驗結果中，從等溫曲線圖和平均每分子占的表面積偏差圖可以發現DOTAP/DPPG在任何混合比例，分子間的排列皆是親和作用，以DOTAP 40% 時分子親和作用最強。而DC-Cholesterol和DPPG的排列則大致是互斥作用，以DC-Cholesterol 20% 時最明顯，其次為60%，在40% 及80% 時則接近理想混合狀況，可見即使有正負電荷互相吸引作用，加入DC-Cholesterol，仍會使分子排列整齊度變差，使平均分子占的表面積變大。混合正電荷及負電荷脂質分子，在水溶液中，除了1:1時會沈澱，其他比例(20%, 40%, 60%, 80%)都會形成微泡，由小角度X光散射及動態光散射量測，發現較中間比例的微泡平均粒徑較大，因正負電荷分子數比例相近時，大部分都形成正負電荷分子對，這類雙鏈分子對更易形成低膜曲率之結構，因此會形成較大的微泡(膜曲率較小)。在DOTAP/DPPG的水溶液混合系統加入短鏈的diC7PC，除了1:1時仍會沈澱，在其他比例，可以將其分散組成直徑約20奈米的平板微胞，但仍會有微泡共同存在。對DC-Cholesterol/DPPG水溶液混合系統，加入短鏈的diC7PC，除了1:1正負電荷比時仍會沈澱，在其他比例也不太能將其分散產生平板微胞，所以主要仍是微泡形態。在20%DOTAP/20%DPPG/30%diC7PC的水溶液混合系統加入30%DPPC，即使1:1正負電荷比時，也可以將其分散組成直徑約20奈米的平板微胞，不會有沈澱，但仍會有微泡共同存在。對20%DC-Cholesterol/20%DPPG/ 30%diC7PC的水溶液混合系統，加入30%DPPC並沒有用，1:1正負電荷比時仍會沈澱，在其他比例主要仍是微泡形態。在加入DNA時，發現在正電荷多於負電時才會和DNA形成複合結構。研究結果顯示利用混合帶正及負電荷脂質分子可以調控其聚集結構，但DOTAP/DPPG的混合系統和DC-Cholesterol/DPPG的混合系統仍有相當不同的特性差異，值得未來從分子排列及交互作用作深入探討。

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.

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