生物膜在許多生物反應上扮演重要的角色，其性質會受到陽離子與脂質組成影響，本論文利用系統性的全原子分子動態模擬，來研究三種不同負電磷脂質比例的脂雙層在含有 Na+、Mg2+、Ca2+ 三種不同陽離子時對膜性質的影響，模擬結果發現大部分的陽離子與磷脂質上磷酸基團(phosphate group) 有較強的作用力，此作用力的大小受到陽離子種類與磷脂質組成比例影響，其中Ca2+ 與磷脂質間有很強的吸引力。當陽離子被吸引到膜面上時，會造成膜面積變小、膜變厚、秩序參數變大、頭基的轉動速度變慢。陽離子與磷脂質間會形成配位，這些配位體間在含有負電磷脂質時會更進一步形成多金屬中心的 clusters ，尤其是在含有 Ca2+ 的情形下。形成這些配位與 clusters 會中和膜面上的負電與減少膜面上的水分子(脫水的現象)，營造膜聚集的有利環境，我們同時推測多金屬中心 Ca2+-cluster 的形成，將有利於膜融合步驟中stalk 結構的生成。 Membranes play key roles in many biological processes, which are affected by cations and lipid compositions. Aimed to systematically understand how the membrane properties are affected by cations and lipid compositions, all-atom long time-scale molecular dynamics simulations were performed for phospholipid bilayers containing three different proportions of negatively charged lipids in the presence of Na+, Mg2+ and Ca2+. Simulations show that cations prefer to bind with the phosphate groups of lipids and the cation-lipid binding affinities depend on cations and lipid compositions. Particularly, the Ca2+ has strong binding affinity with lipids. Binding of cations to lipids leads the lipid bilayers to be smaller in its lateral area, thicker, more ordered and slower rotation of lipid head groups. Cations form complexes with lipids and these complexes further assemble to form various multiple-cation-centered clusters in the presence of anionic lipids, in particular, the Ca2+. Formation of cation-lipid complexes as well as clusters dehydrate and neutralize the anionic lipids, creating an energy favorable environment for membrane aggregation. We propose the formation of Ca2+-phospholipid clusters across apposed lipid bilayers are a kinetically and thermodynamically favorable pathway for the stalk state formation in membrane fusion.
