The Interaction between Surfactants and Lipid Aggregates: a Dissipative Particle Dynamics Study

微脂粒是由脂質分子所組成的囊胞，其雙層膜的構造類似生物體內具有滲透性的細胞膜，此外，微脂粒擁有良好的生物可分解性與生物相容性，因此成為理想的藥物載體。然而人體內有許多的生物型界面活性劑會破壞囊胞之穩定性，因此，兩者之間的作用向來都是人們關心的問題。本文使用耗散粒子動力學法來研究界面活性劑與囊胞的交互作用，探討界面活性劑的濃度及親疏水性對囊胞結構及雙層膜強度的影響。擬結果顯示，隨著界面活性劑濃度的增加，囊胞會因界面活性劑的加入而增大，但初始仍維持完整球型構造。當界面活性劑在囊胞外之溶液中達到了臨界微胞濃度，隨後囊胞結構遭到破壞而產生破洞，此時再加入界面活性劑，就會造成脂質分子開始離開囊胞，與界面活性劑共同形成混合微胞，進而使囊胞完全瓦解。根據上述結果，在定性上可得到界面活性劑之臨界微胞濃度<囊胞穿孔濃度<囊胞溶解濃度之關係。們亦同時發現，親水性高的界面活性劑溶解囊胞的能力較好，在相對較低的濃度就可以溶解囊胞，所形成之混合微胞尺寸較小並均勻分佈於溶液中。但值得注意的是，過於親水的界面活性劑傾向留在溶液中，僅有少數分子加入囊胞，所以在我們研究的濃度範圍內，並未呈現破壞囊胞結構的現象。反之，過於疏水的界面活性劑幾乎全數進入囊胞內，使得囊胞體積持續增大至變形為圓柱、甜甜圈或薄片雙層結構。囊胞的原始結構雖已被破壞，但脂質分子與界面活性劑傾向共同形成一巨大聚集體，而非傳統觀念中之均勻分佈的小尺寸混合微胞。胞因為界面活性劑的加入而穿孔、溶解，表示囊胞脂雙層的結構強度受到影響。本研究發現，在囊胞結構未被破壞前，界面活性劑的加入可以增大囊胞的內部水區。為了測試界面活性劑對囊胞結構強度的影響，我們執行兩種分析工作，分別為計算囊胞脂雙層的表面張力以及在囊胞內部加水增壓的試驗。結果顯示，疏水性越強的脂質分子所形成之囊胞可承受的壓力差越大，即代表表面張力越大。而界面活性劑的加入，會降低囊胞之表面張力，使囊胞抵抗內外壓力差的能力變弱。們也探討由界面活性劑與脂質分子共同形成之混合微胞的性質，研究顯示界面活性劑疏水性越高越傾向與脂質分子聚合，隨著界面活性劑總濃度提高，混合微胞的數目卻隨之變少，即界面活性劑的加入，促使脂質分子進一步聚集，並且界面活性劑分佈在混合微胞中與溶劑間的分佈係數為一定值，符合理想溶液的預測。當我們提高界面活性劑與脂質分子疏水鏈段間的不相容性，則可以觀察到混合微胞內原本均勻分佈的界面活性劑與脂質分子發生離析的現象，且疏水鏈段越長的界面活性劑此現象越明顯。A liposome is a vesicle composed of lipid monomers. Its structure is similar to the permeable cell membrane which exists in organisms. Liposomes are considered ideal drug-carriers due to their high biodegradability and biocompatibility. However, many kinds of biosurfactant existing in human body could decrease vesicle stability, so the reaction between vesicles and biosurfactants has been highly concerned by researchers. In this work, simulations based on dissipative particle dynamics are performed to study the interactions between vesicles and surfactants. The effects of concentration and hydrophobicity of surfactants on the structure and stability of vesicles are investigated.imulation results show that as the concentration of surfactants (s) increases, vesicle increases in size and remains spherical structure at first. Then the surfactants in the bulk solution start to aggregate, i.e. surfactant concentration in the bulk phase reaches its critical micelle concentration (scmc). After that vesicle begins to perforate (sp). Further addition of surfactants results in the beginning of the dissolution process (sd). The lipid molecules start to leave the vesicle and join the surfactant micelles to form mixed micelles. Eventually the total collapse of the vesicle is observed. Therefore, scmc<sp <sd.e have also found that surfactants with greater hydrophilicity can dissolve vesicles more easily. The resulting mixed micelles are comparably small in size and distribute homogeneously with the solution. However, surfactants with excessive hydrophilicity tend to stay in the bulk solution and only a few of them enter into the vesicle. As a consequence, the structure of the vesicle remains intact for all the surfactant concentrations we have studied. On the other hand, surfactants with extreme hydrophobicity tend to go into the vesicle, therefore, the size of the vesicle continues to grow as s increases. Instead of forming discrete mixed micelles, the lipid molecules and surfactants become one large aggregate taking the shapes of cylinders, donuts, bilayers, etc.esicles formed by lipid molecules with higher hydrophobicity possess greater surface tension energy and thus have a smaller inner water zone. The effect of the addition of surfactants on the surface tension of the vesicle membrane is also studied in this work. Two analyses have been made: direct calculation of the surface tension of the vesicle and increase of the pressure inside the vesicle by adding water. It is found that the incorporation of surfactants into the vesicle leads to decrease in the surface tension of the vesicle membrane.e have also studied the physical properties of the lipid-surfactant mixed micelles. As surfactant concentration increases, number of aggregates decreases. This result indicates that the addition of surfactants enhance the aggregation of lipid molecules which is counter-intuitive. In addition, the incompatibility between the hydrophobic tails of surfactants and lipids give rise to segregation within the mixed micelles. The degree of segregation goes through a first-order transition as incompatibility enhances.摘要 IBSTRACT III錄 V表目錄 VI一章 緒論 1 1.1 簡介（INTRODUCTION） 1 1.2 界面活性劑（SURFACTANT） 2 1.3 囊胞（VESICLE） 7 1.4 界面活性劑與囊胞之作用 11 1.5 表面張力 15二章 模擬原理與方法 17 2.1 耗散粒子動力學 17 2.2耗散粒子動力學原理 19 2.3模擬方法 27 2.3-1 初始系統設定 27 2.3-2 lipid參數設定 28 2.3-3 Surfactant參數設定 28三章 結果與討論 30 3.1 混合微胞 (MIXED-MICELLE) 30 3.2 界面活性劑對於囊胞的影響 40 3.3 囊胞脂雙層的強度 69四章 結論 77考文獻 7