膜融合在細胞間物質傳遞、神經傳送素釋放、以及病毒感染的過程中扮演重要的角色。其反應機制與能量變化尚未被充分了解。本篇論文採用全原子分子動態模擬法研究由鈣離子誘發兩個周圍充滿水分子的palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE)微胞自發融合的完整過程。本模擬系統類似兩個囊胞間可能開啟融合過程的小接觸帶。模擬結果顯示鈣離子有能力催化POPE微胞融合，但在類似的鈉離子模擬系統中，即使模擬時間更長，也沒有觀察到微胞融合的發生或是兩個微胞距離被拉近的情況。我們藉由energy landscape來解釋融合的反應機制。兩個微胞之間形成鈣離子-磷脂質的cluster誘發融合。由鈣離子-磷脂質的cluster所生成的prestalk state因磷脂質尾端暴露於水溶液中，所以自由能都高於接下來的stalk state 及hemifused-like state。因此，prestalk state的生成是融合過程中的速率決定步驟。本篇研究發現生成prestalk到stalk state之間的dewetting transition。Dewetting transition 決定stalk state的形成。本篇研究指出，在高水合的環境下，dewetting transition是形成stalk的關鍵步驟。Membrane fusion plays a key role in intracellular trafficking, neurotransmitter release, and viral infection. The molecular mechanism as well as energy landscape is not well understood. We have employed all-atom molecular dynamics simulations to study the entire fusion process of two hydrated 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE) micelles induced by Ca2+ in a spontaneous fashion. This simulation system mimics the small contact zone between two large vesicles at which fusion may be initiated. Simulations reveal the Ca2+ is capable to catalyze the fusion of POPE micelles, whereas similar simulation with longer simulation time performed with Na+ does not observe the occurrence of fusion or even close contact of two micelles. We characterized the underlying molecular mechanism of fusion in terms of free energy landscape. The fusion is induced by the formation of inter-micelle Ca2+-lipid cluster. A prestalk state with solvent-exposed lipid tails involving in the inter-micelle Ca2+-lipid cluster has a higher free energy than the following stalk and hemifused-like states. In turn, the formation of the prestalk state is the rate-limiting step of fusion. A dewetting transition occurring in between the formation of prestalk and stalk states is observed. The formation of stalk state is determined by the dewetting transition. Our study indicates, for high hydration, the dewetting transition is the critical step in the stalk formation.
