囊胞與支撐性脂雙層膜的動力學與機械性質研究

支撐性脂雙層膜是一個針對細胞膜模擬非常熱門的模型，並且有希望在未來作為醫療設備和仿生技術的應用。但是關於支撐性脂雙層膜的生成機制並未被完全了解。在本研究中利用耗散粒子動力學法進行單顆、單球殼的小顆囊胞瓦解塗佈在親水性基板上的探討。根據脂質尾巴的親疏水性和囊胞的大小的不同，囊胞在瓦解塗佈的過程中可以區分成三種型式，分別為不瓦解、部分瓦解、以及完全瓦解的囊胞。根據結果可以得到一個形態學上的相圖，其中顯示當囊胞上脂質的尾巴的疏水性較弱以及本身較小顆的時候，在瓦解塗佈在基板的過程中囊胞容易完全瓦解。進一步能夠發現，囊胞瓦解塗佈在基板上的結果，可以經由調整脂雙層膜的表面張力以及脂質分子的親水性頭基和基本的接觸力大小來改變。另外若是多顆囊胞與親水性基板一同作用，囊胞之間互相融合的可能性多餘囊胞瓦解塗佈在基板上。第二部份是經由耗散粒子動力學法針對小顆單殼層的囊胞在溫度改變時的相變進行探討。由脂質分子自組裝行程的囊胞，其脂雙層膜存在從膠體態到波浪態的前相轉移，以及波浪態到液態的主相轉移。囊胞在低溫的時候外觀具有多面體的特性，隨著溫度提升漸漸變得越來越像球體，單是當溫度更進一步提高，囊胞的形狀開始變得不規則。當溫度增加的時候囊胞的大小也增加，但是膜本身的厚度卻是下降的。而囊胞的主相轉移溫度可以藉由大小或者厚度對溫度做圖，這條曲線的反曲點對應到的溫度即為主相轉移溫度。囊胞的結構特性也進一步的獲得分析，其表面膜的內層與外層是不對稱的。脂質分子尾巴的長度以及兩側脂質分子頭基面積密度都會隨著溫度的上升而減少。然而平均脂質分子體積在低溫的時候會隨著溫度的升高而增加，在高溫時則相反。針對脂雙層膜的機械性質也做了分析，水通過脂雙層膜的穿透性隨著溫度的提升而有了指數型的增加；脂雙層膜的表面張力在主相轉移溫度有最大值；而彎曲模數和拉伸模數的最小值則出現在主相轉移溫度附近。這些結果與一般實驗中脂雙層模所觀察到的現象一致，表示相轉移的現象也能夠在單殼層的囊胞上展現。最後一部份則是利用耗散粒子動力學法探討不同形狀特色（不同疏水端長度、彎曲的疏水端、不對稱的疏水端）所形成的支撐性脂雙層模。脂質分子在平面上的擴散（Dx）或者是在不同層之間的翻轉（FF），不論在膠體態或者液態都會隨著溫度的上升而提升，並且可以用阿瑞尼亞士方程式來表示。在脂質分子疏水鏈段的碳鏈若是飽和的直鏈，不論兩條輸水鏈段對稱或者不對稱在形態上可以觀察到三個區間；若是疏水鏈段具有不飽和的碳鏈（彎曲），就只能觀察到兩個區間。而擴散或是翻轉的行為都會隨著疏水鏈段長度的縮短或是彎曲有增加的趨勢。機械性質上，彎曲模數（KB）和拉伸模數（KA）和第二部份的單殼層囊胞一樣，在相轉移溫度附近有最小值，並且隨著疏水鏈段的增長而減少；隨著疏水鏈段彎曲的增加而上升。而彎曲模數、伸展模數、以及脂雙層膜厚度之間的關係也與K_B=βK_A h^2這個關係式符合，並且β在膠體態下會遠小於液態。而疏水鏈段不對稱的脂質分子形成的支撐性脂雙層膜，則會與碳鏈數相近的對稱型脂質分子有接近的機械與動力學性質。

關鍵字

脂質分子；自組裝；耗散粒子動力學法；囊胞；支撐性脂雙層膜；藥物傳遞

並列摘要

Supported lipid bilayers (SLBs) are popular as model systems for cell membranes and are promising for future applications in diagnostic devices and biomimetics. However, the mechanism of SLB formation is not fully understood. In this study, the deposition process of a single small unilamellar vesicle on hydrophilic supports is explored by dissipative particle dynamics. Dependent on lipid tail hydrophobicity and vesicle size, there exist three distinctive pathways of vesicle deposition, involving non-disintegrated, partially disintegrated, and completely disintegrated vesicle. A morphological phase diagram is presented and it reveals that a vesicle with weak tail hydrophobicity and small size tends to be completely disintegrated upon deposition. Moreover, our simulation results clearly indicate that the deposition process of a vesicle onto the solid surfaces can be adjusted by altering the vesicular membrane tension and the interaction strength between the lipid head and solid support. Finally, the deposition process of multiple vesicles on hydrophilic solid surface is also investigated. The result shows that the fusion of vesicles have a tendency to hinder the formation of a SLB. The phase behaviors and membrane properties of small unilamellar vesicles have been explored at different temperatures by dissipative particle dynamics simulations. The vesicles spontaneously formed by model lipids exhibit pre-transition from gel to ripple phase and main transition from ripple to liquid phase. The vesicle shape exhibits the faceted feature at low temperature, becomes more sphere-like with increasing temperature, but loses its sphericity at high temperature. As the temperature rises, the vesicle size grows but the membrane thickness declines. The main transition (Tm) can be identified by the inflection point. The membrane structural characteristics are analyzed. The inner and outer leaflets are asymmetric. The length of the lipid tail and area density of the lipid head in both leaflets decrease with increasing temperature. However, the mean lipid volume grows at low temperature but declines at high temperature. The membrane mechanical properties are also investigated. The water permeability grows exponentially with increasing T but the membrane tension peaks at Tm. Both the bending and stretching moduli have their minima near Tm. Those results are consistent with the experimental observations, indicating that the main signatures associated with phase transition are clearly observed in small unilamellar vesicles. In chapter 5, dynamic and mechanical properties of SLBs are explored by dissipative particle dynamics simulations for lipids with different architectures (chain length, kink, and asymmetry associated with lipid tails). It is found that the lateral diffusivity (Dx) and flip-flop rate (FF) grow with increasing temperature in both gel and liquid phases and can be described by an Arrhenius-like expression. Three regimes can be clearly identified for symmetric and asymmetric saturated lipids but only two regimes are observed for kinked lipids. Both Dx and FF grow with decreasing tail length and increasing number of kinks. The stretching (KA) and apparent bending (KB) moduli exhibit concave upward curves with temperature and the minima are attained at Tm. In general, the minima of KA and KB decrease with the chain length and increase with number of kinks. The typical relation among the bending modulus, area stretching modulus, and bilayer thickness is still followed, K_B=βK_A h^2 and β is much smaller in the gel phase. The dynamic and mechanical properties of lipids with asymmetric tails are found to situate between their symmetric counterparts.