為了瞭解邊緣貼附於疏水基板上而懸浮於奈米孔洞中之脂雙層受到AFM探針壓迫和刺入過程的現象與機制，我們使用分子動力學模擬(molecular dynamic simulation)進行研究。本次工作從脂雙層基本性質的研究開始，模擬一大片的脂雙層(lipid bilayer in bulk) (無基板支撐)在溶劑中的行為，我們計算膜厚度、單位脂質面積，以及秩序參數(order parameter)，發現從低溫到高溫依序出現傾斜膠態(tilted gel state， )、叉合膠態(interdigitated gel state， )，以及液態(liquid state， )，除了膠態到液態的主要相變化(main transition)之外，亦觀察到傾斜膠態和叉合膠態的相變化。此相變化研究的結果與許多文獻類似，故可說明本研究的模型與設定之真實性。第二部份為懸浮脂雙層的AFM壓刺研究，將脂雙層自然的成長於疏水基板上，使其懸空於孔洞中，並放置一足夠長時間以達到穩定狀態，再將一探針刺入脂雙層。孔洞形狀設計為側壁與基板上方垂直，探針則為一半圓球位於孔洞正中間。從探針接觸脂雙層直到脂雙層完全破壞為止，可以歸納出五個階段：1.脂雙層受力彎曲成圓弧形狀，而脂雙層邊緣在克服阻力之後於基版側璧上滑移，2.脂雙層邊緣達到孔洞底部之後滑移現象停止，彎曲過程則持續進行，3.脂雙層在中央偏左的區域發生底部單層破裂，此區域脂質分子混亂分佈，4.破裂區域脂質分子重新排列成叉合膠態的規律結構，此結構改變的效應將擴散至鄰近區域而造成大面積的相變化行為，5.叉合膠態與傾斜膠態區域的連接處不穩定，最終造成脂雙層的完全破裂。脂雙層在基板側壁上的滑動現象首次提出且為出乎意料的結果，此機制消除了垂直的孔洞邊緣下脂雙層的應力集中，而避免脂雙層於側壁上的快速破裂。最後，我們並測量懸浮脂雙層的彈簧常數、最大探針受力，以及最大探針刺入深度，並和實驗值比較，發現非常的吻合，更進一步的說明此次研究對於壓刺過程之現象及破壞機制的歸納是值得信任的。研究中引入Quasi-2D以及phantom solvent等較為新穎的模型設計，在經過此次工作的驗證之後，將可以進一步運用於脂雙層研究領域中的其他工作。

We perform molecular dynamic simulations to understand the behavior and mechanism of AFM indentation through a lipid bilayer which is suspended by hydrophobic substrate on a nano pore. This work starts from the study of basic properties of lipid bilayer. By simulating lipid bilayer in bulk with solvent environment, we calculate membrane thickness, area per lipid, and order parameter. Three states are found from low temperature to high temperature: tilted gel state, interdigitated gel state, and liquid state. Besides main transition which is from gel state to liquid state, we also observe transition from tilted gel state to interdigitated gel state. The work in phase transition consists with many previous works, which demonstrate the reality of our model and setup. The second part of the work is AFM indentation of suspended lipid bilayer. We build the system with suspended lipid bilayer on a nano pore. After a long period of equilibrium, bilayer is indented by AFM probe. The shape of the side wall of substrate is a straight cliff with 90 degree at its corners. The probe is a half sphere located at the center of the pore. From the contact between the lipid bilayer and the probe, we conclude 5 stages: 1. the pressed lipid bilayer bends to arched curve, while the edges of lipid bilayer slide on the side wall of substrate. 2. The edges of lipid bilayer reach the end of pore on the side wall and stop sliding, while bending continuously proceeds. 3. The breaking at bottom monolayer happens in the center region, which cause chaotic distribution in the region. 4. Lipids at the region of monolayer breaking reform into interdigitated gel structure. 5. The fracture happens at the conjunction between transformed region and non-transformed region due to incongruence between the two regions. The sliding mechanism is mentioned first time and really surprises us. This mechanism eliminates the stress concentration between side wall of substrate and edge of lipid bilayer, and avoids the early breaking at the contact surface. At the end, we calculate the spring constant, maximum force on probe, and maximum depth of indentation. We find the data are in good agreement with experimental result. This further verifies the validity of our study. In the research, we employ some new methods such as Quasi-2D and phantom solvent which can be used in other researches in this field.

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