本研究利用分子動力學模擬在壓痕試驗中自由懸浮於溶劑中的脂質雙層，並且探討在壓痕試驗中探針與脂質之間的作用力對脂質雙層結構的影響。藉由計算壓痕過程中脂質雙層的局部的物理性質變化，我們證實了探針下壓而使脂質雙層破裂的原因不僅是因為雙層結構的局部薄化而使脂質尾端自由能上升；雙層結構的局部延展也會使得脂質尾端暴露於水溶液當中而使脂質尾端粒子自由能進一步增加，這兩種原因皆提高了微孔洞的形成的機率而使破裂發生。而在探針的縮回過程中，我們發現，假如探針與脂質尾端之間的作用力不足以使脂質尾端吸附於探針上，脂質分子會在破裂區域重新排列成親水性的雙層邊界而最終在脂質雙層中留下親水性孔洞，且探針上不會出現任何的殘餘吸附脂質。反之在探針的縮回的過程中脂質尾端吸附於探針之上，則最終脂質雙層可回復到自由懸浮的狀態，其物理性質與壓痕前的脂質雙層幾乎相同，且可在探針上觀察到殘餘的吸附脂質，而其數量則取決於探針與脂質頭部間的作用力；此作用力越強，則探針上將留下較多的殘餘吸附脂質，這些結果可以幫助我們於藥理學上尋找適合的奈米注射裝置。
本研究進一步觀測探針縮回時的受力情形並與探針與脂質之間的作用力關係做比對，發現在相同的壓痕速度下，當探針與脂質尾端之間的作用力較強時，在探針縮回過程中會測得較大的探針最大吸附力；反之假如探針與脂質尾端之間的作用力較弱，則會在探針縮回的過程中測得較小的探針最大吸附力。這些結果表明，我們可以利用AFM實驗所得到的正向力-位移變化曲線來判定探針與脂質間作用力的強弱關係，並做為在相關脂質雙層的量測實驗中關於探針材質選用的一個參考。

We study the indentation test of a free-standing lipid bilayer by molecular dynamics simulation, and discuss the effect of the interaction between the probe and the lipids on the bilayer structure. By calculating the local physical quantities of the lipid bilayers in the indentation process, we confirmed that the cause of bilayer rupture is not only because bilayer local thinning make the free energy of the lipid tails increase, bilayer local extension also make the lipid tails exposure to solvent and further increase the free energy of the lipid tails. These two reasons both increase the probability of micro voids formation of the lipid bilayers. In the retraction process, we found that if the interaction between the probe and the lipid tails is insufficient to make lipids adsorbed on the probe, the lipid molecules tend to rearrange to form hydrophilic bilayer edges in the rupture regions and eventually leave a hydrophilic pore in the bilayer, and no residual lipids were found on the probe. Conversely, if the lipid tails are adsorbed by the probe in the retraction process, the lipid bilayers can revert to a free-standing state, and the physical quantities of the lipid bilayers before and after the indentation are almost identical. Besides, we found that there are some residual lipids were adsorbed by the probe, and the number of the residual lipids depends on the interaction between the probe and the lipid head groups, the stronger the interaction is, the more number of residual lipids were adsorbed by the probe. These results can help us to find a suitable pharmacologically nanoinjectors.
Furthermore, we investigated the relationship between the force-indentation curve and the interaction between the probe and the lipids. As expected, we observe that when the interaction between the probe and the lipid tail is stronger, the lager maximum attractive force can be measured in the retraction process at the same indentation speed. These results show that we can use the force –indentation curve obtained from AFM experiments to define the magnitude of the interaction between the probe and the lipids, and help us to select the proper probe materials in the relevant AFM experiments.

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