The Interaction between Nanoparticles and Supported Lipid Bilayers

奈米科技是近年來非常重要的發展，由於其高表面體積比和量子的效應，在食品保健、再生能源和電子產品等的應用相當廣泛。然而根據最新的研究指出，奈米粒子其實是可能具有細胞毒性的，不管是由皮膚接觸或者呼吸道和消化系統進入到人體內時，因為其顆粒微小（0.1-100 nm），所以能夠以很快的速度擴散至全身，在與體內的細胞接觸後會造成細胞扭曲、破裂甚至死亡，因此奈米粒子與細胞膜作用的研究非常重要。 本研究中，我們利用耗散粒子動力學法模擬奈米粒子對支撐性脂質雙層膜的影響。支撐性脂質雙層膜(Supported lipid bilayers)是由脂質雙層膜吸附在一親水的基材上，相對於漂浮的膜，其擁有較高的穩定性，因此常應用於模擬真實細胞膜的模組。我們發現脂質分子吸附於奈米粒子上的程度隨著溫度會有所變化，隨溫度上升吸附的脂質也越多，且分別在前相轉移溫度(Pre-transition temperature)和相轉移溫度(Main transition temperature)有著峰值，之後則呈現下降至某一定值。奈米粒子的疏水度需要大於某一臨界值才會對支撐性脂質雙層膜造成影響，此臨界值是溫度的函數。在超過此臨界值後，其對膜的作用則不隨疏水度而改變。加入的奈米粒子粒徑越小和數量越少，則其單位表面積上所吸附的脂質分子密度越高；相較之下，一般溫度下大粒徑和大量的奈米粒子的吸附密度較低，但是在高溫時，有機會造成脂質雙層膜的破洞，從而能得到更高的吸附密度。最後我們利用Johnson- Mehl – Avrami - Kolmogorov（JMAK）方程式來分析各種條件下脂質雙層膜的破洞面積變化速率，發現其反應的機制與一維的異相結晶結果一致，並且不會隨著奈米粒子粒徑大小、親疏水性和濃度而改變。 本研究成果能在未來作為生醫材料進入人體時，減低對人體造成的負擔；也可以在應用做殺菌劑或抗癌藥物時，充分預測反應最適溫度、反應速度等等因素，達到節省成本及時間的效果。Nanotechnology is the science of the very small and involves the manipulation of matter at the atomic or molecular level. Nanoparticles possess high surface-to-volume ratio and quantum effects and are broadly employed in the developments of electronics, renewable energy and medication. However, latest research has demonstrated that nanoparticles may exhibit cytotoxicity. Because of its small size, nanoparticles can interact with the cell membrane resulting in perforation or death of cells. As a consequence, the study of the interaction between nanoparticle and cell membrane is of great importance. In this work, the dissipative particle dynamics is employed to investigate the mechanism of nanoparticle-supported lipid bilayer (SLB) interaction. SLB is an ideal model for cell membrane since it is more stable than a freely suspended membrane. It is found that lipids tend to adsorb onto nanoparticles as temperatures increases and the adsorption curves exhibit two peaks at the pre-transition temperature and the main transition temperature. Furthermore, our results show that the hydrophobicity of a nanoparticle needs to exceed a critical value before the nanoparticle-SLB interaction takes place and the critical hydrophobicity varies with temperature. We also find that the adsorption area density of lipids on small-sized nanoparticle is greater than that of large-sized counterpart. However, as temperature increases, large-sized nanoparticles have the ability to perforate the lipid bilayer. Johnson-Mehl-Avrami-Kolmogorov equation is used to correlate the variation of the perforation surface area with time. The results reveal that the perforation mechanism of the membrane is essentially the same as the one dimension, heterogeneous nucleation process and is independent of the size, hydrophobicity and number of nanoparticles in the system. This work can be applicable to prevent harmful effects of nanoparticles to our body. It can also be used to predict the reaction rate and reaction temperature to maximize the cytotoxicity of the nanoparticles when it is applied as an anticancer drug or disinfectant.口試委員會審定書 誌謝 i 摘要 ii ABSTRACT iii CONTENTS v LIST OF FIGURES vi LIST OF TABLES vii Chapter 1 緒論 1 1.1 支撐性脂質雙層膜 .1 1.2 脂質雙層膜的相行為 .3 1.3 奈米粒子的細胞毒性 5 Chapter 2 模擬原理與方法 11 2.1 耗散粒子動力學法(Dissipative Particle Dynamics ; DPD) 11 2.2 DPD原理 13 2.3 作用力參數和Flory-Huggins Theory 19 2.4 模擬方法 21 2.4.1 DPD附加的力 21 2.4.2 系統參數設定 21 2.4.3 Lipid作用力參數設定 22 2.4.4 奈米粒子和親水板的作用力參數設定 24 Chapter 3 結果與討論 26 3.1 奈米粒子與支撐性脂質雙層膜的製備 26 3.2 小粒徑奈米粒子與支撐性脂質雙層膜的作用 29 3.3 大粒徑奈米粒子與支撐性脂質雙層麼的作用 42 Chapter 4 結論 50 Chapter 5 參考文獻 5