| 摘要: | 細胞膜為細胞之重要胞器之一。此主要由磷脂質、蛋白質，及碳水化合物組成之膜狀結構亦構成了細胞隔絕外來有害物質之第一道屏障。做為與外界環境作用之關鍵胞器，細胞膜之物理性質如軟硬度、相態、動態行為、及對胜肽作用等皆受膜組成成分影響。在以上性質中，探討後兩者能對了解某些神經相關疾病之機制做出貢獻。細胞膜之動態行為也容易隨著膜組成變動而受到影響。磷脂質之親水頭基與疏水碳氫鏈若產生改變，會影響不同尺度膜運動行為之運動速度如膜波動或膜內脂質分子運動等。除了膜動態性質外，本研究亦利用澱粉樣胜肽β作為媒介以更了解細胞膜與胜肽間作用；根據先前文獻指出阿茲海默症可能為澱粉樣胜肽β之寡聚體及患者腦部氧化共同作用下造成。由氧化造成之膜內碳氫鏈變異，對澱粉樣胜肽β如何與神經細胞膜作用可能會是決定性因素。我們從中子自旋回聲及準彈性中子散射之實驗結果得知，脂質膜之動態行為受到碳氫鏈飽和度變異之影響甚劇:脂質分子之碳氫鏈飽和度較高，脂質分子在膜內之運動速度會降低；而在我們之觀察範圍內，頭基變異對整體膜動態行為只造成些微影響。在胜肽對膜作用方面，我們亦發現澱粉樣胜肽β寡聚體對膜作用與氧化引發之膜組成變異以及銅離子有關。根據我們小角度X光散射以及寡聚體螢光檢測之數據，澱粉樣胜肽β寡聚體之貼附行為會引起氧化後之脂質膜外層之明顯結構變化；然而，我們卻沒有從脂質膜完整性實驗中觀察到任何由澱粉樣胜肽β寡聚體引發之脂質膜上缺陷或孔洞，且氧化後之脂質膜在與澱粉樣胜肽β寡聚體作用後亦維持其原本之完整性；由此可知，此交互作用應為非破壞性作用。整體而言，脂質膜之組成變異無論對膜動態行為及胜肽與膜作用都有顯著之影響:若脂質膜之飽和度上升，其在膜內之分子運動速度將變慢；而由氧化引發之碳氫鏈裂解、飽和度上升也使澱粉樣胜肽β寡聚體對脂質膜作用更顯著。由此可知，膜之飽和度是影響脂質膜動態行為以及胜肽對膜作用之關鍵因素。;Cell membranes are an essential portion for cells to operate functionally, keep the viability of organisms, and hold abilities to receive, resist, or interact with molecules outside cells. Among the diverse properties of membranes, composition is a crucial one for their biological functions; the rigidity, phases, dynamics, and interaction with peptides are highly related to it. Among these aspects, exploring the latter two may contribute to the understanding of the mechanisms of some neurological diseases. Because of the mobility difference of lipids, compositional variations would modulate membrane dynamics in various spatial scales. On the other hand, we employed amyloid β peptides (Aβ) to investigate the membrane-peptide interaction. According to previous studies, Alzheimer’s disease could be the combined result of Aβ aggregation and oxidative stress, and Aβ-membrane interactions could be different once the composition of membranes was varied by the hydrocarbon chain oxidation. From our inelastic neutron scattering results, we found that membrane dynamics in various spatial scales were highly related to lipids’ molecular configuration in hydrocarbon chains but not in head groups. On the Aβ-membrane interaction aspects, we found that the interaction between membranes and Aβ aggregates was highly related to membrane compositions and the presence of Cu2+. From X-ray scattering and fluorescence data, we knew that Aβ oligomers would provide structural impacts on outer leaflets of membranes by Aβ attachments and shallow insertions. However, membranes retained their structural integrity after the interaction with Aβ aggregates, and compositional variations from oxidative treatments also could not affect the integrity of lipid membranes in the event of Aβ oligomers-membrane interaction. Altogether, we find that the increase of saturation degrees affected their dynamics in wide spatial scales and carry out the structure-disrupting membrane-peptide interactions. |
