囊胞之物理性質及融合程序受界面活性劑影響之探討

Abstract

囊胞是由脂質所組成的雙層膜球型聚集體，其構造類似生物體的細胞膜，此外囊胞擁有良好的生物相容性及生物降解性，因此廣泛應用於藥物釋放載體以及模擬細胞膜的各種反應。當囊胞進入生物體時，會受到生物型界面活性劑影響，因此兩者之間的作用向來是研究囊胞的必備工作。本研究利用耗散粒子動力學法來研究囊胞與界面活性劑的交互作用，探討低濃度之界面活性劑下，囊胞之物理性質的變化以及受界面活性劑影響後之囊胞其融合程序的影響。 模擬結果顯示，界面活性劑會分佈在溶劑區以及脂雙層膜中，隨著界面活性劑濃度越高，分佈在脂雙層的界面活性劑數量越多。界面活性劑為一種兩性分子，進入脂雙層時會降低囊胞的表面張力，直至表面張力為零。以表面張力等於零為分界點，界面活性劑一開始進入囊胞時，會增加脂雙層的疏水鏈段排列整齊度和膜厚，符合自發性囊胞的趨勢；但是當囊胞表面張力被鬆弛至零時，再加入的界面活性劑會破壞脂雙層疏水鏈段的排列，並使囊胞延伸變形，膜的厚度也隨之下降。 本研究發現在我們選定不同疏水性質之界面活性劑的探討中，疏水性較高的界面活性劑傾向進入囊胞脂雙層中，對囊胞的影響也越劇烈。疏水性較高的界面活性劑，在相對低的濃度即可使囊胞之表面張力下降至零，而脂雙層的疏水鏈段排列整齊度和厚度先上升後下降的趨勢也較為明顯，且最高點發生在相對低的界面活性劑濃度。此外，我們亦發現囊胞的物理性質變化與界面活性劑在脂雙層上的數量存在一定關係，意即在我們選定的範圍內，無論界面活性劑的疏水性質如何，在膜上之界面活性劑的數量控制著囊胞的物理性質。 小顆囊胞的系統其每單位脂質擁有的膜上界面活性劑數量較多，經由固定系統脂質數量但藉由塞水改變囊胞之表面張力的實驗，我們發現隨著表面張力的增加，界面活性劑進入脂雙層的數量也增加，意即表面張力是驅使界面活性劑進入囊胞的驅動力之一。界面活性劑的加入使得囊胞表面張力下降，當脂雙層中界面活性劑足以讓囊胞表面張力為零時，囊胞之疏水鏈段整齊度較原始囊胞來得小，且膜厚變薄了；但脂雙層中界面活性劑不足讓囊胞表面張力下降至零時，與原始囊胞相較之下，囊胞的疏水鏈段整齊度和膜厚增加了，符合自發性囊胞之趨勢。 於是我們推斷囊胞之物理性質的變化有兩種機制：加入界面活性劑後，表面張力呈現下降趨勢時，脂雙層的疏水鏈段整齊度和膜厚會上升；當脂雙層擁有一定量的界面活性劑後，囊胞表面張力為零之後，脂雙層的疏水鏈段整齊度和膜厚便下降。 由囊胞的融合結果，我們發現與界面活性劑作用後的囊胞，隨著界面活性劑濃度的增加，融合完成所花費的時間越長。根據前述的物理性質分析，隨著界面活性劑濃度增加，囊胞的表面張力隨之逐漸下降，此現象符合文獻所提到表面張力與融合程序的關係：表面張力越大的囊胞系統，融合的速率也越快；反之，表面張力越小的囊胞系統，即受到較高濃度之界面活性劑影響的囊胞系統，完成融合的時間就越久。

Vesicles are spherical aggregates composed of lipid monomers. Its structure is similar to the cell membrane which exists in organisms. Vesicles are widely used for drug delivery carriers and simulation of cell membrane behavior due to their high biodegradability and biocompatibility. However, vesicles are affected by biosurfactants when they enter organisms, so the interactions between vesicles and surfactants have been an important work in studying vesicles. In this work, simulations based on dissipative particle dynamics are performed to study the interactions between vesicles and surfactants. The effects of surfactants on the physical properties and fusion process of vesicles in low surfactant concentration are investigated. Simulation results show that surfactants distribute in the bulk solution and the bilayer of the vesicle. As the concentration of surfactants (φs) increases, the amount of surfactants into the membrane increases. A surfactant is a kind of amphiphile, and the incorporation of surfactants into the vesicle causes decrease in the surface tension of the vesicle membrane until the surface tension becomes zero. The order parameter and thickness of vesicle increase as surfactants enter into the vesicle initially, and the trend corresponds to that of spontaneously formed vesicles. After the surface tension of membrane equals zero, adding more surfactants disrupts the arrangement of lipid tails, and then makes the vesicle become deformed and ductile, so the thickness of membrane decreases. In our research of surfactants with different hydrophobicity, surfactants with excessive hydrophobicity tend to enter into the vesicle, and therefore the effect on the vesicle is more severe. Surfactants with excessive hydrophobicity cause the surface tension of vesicle to become zero at relatively low concentration. In addition, the trend of order parameter and thickness of vesicle which increases initially and then decreases is more obvious, and the maximum occurs at relatively low concentration. Furthermore, we have found that there is a certain relationship between the physical properties of vesicle and the amount of surfactants on the membrane, i.e. the physical properties of vesicle depend on the amount of surfactants on the membrane irrespective of the surfactant's hydrophobicity. The number of surfactants per lipids is more in small vesicle. By fixing the number of lipids in the system and increasing the pressure inside the vesicle by adding water, it is found that the amount of surfactants on the membrane increases as the surface tension increases. As a consequence, the surface tension is a driving force of surfactants to go into the vesicle. Adding surfactants leads to decrease in the surface tension of vesicle. When the number of surfactants is enough for the surface tension to become zero, the order parameter and thickness decrease compared to the original vesicle. On the other hand, the order parameter and thickness increase when the number of surfactants is not enough for the surface tension to become zero. This phenomenon corresponds to the trend of spontaneously formed vesicle. Fusion results show that the fusion time of vesicles which is affected by surfactants is longer as surfactants concentration increases. The surface tension of vesicle decreases as surfactants concentration increases, and this result is consistent to the previous studies, that is, vesicles of high surface tension fuse faster than those of low surface tension.