期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 26, 期 3, 页码 485-494出版社
IOS PRESS
DOI: 10.3233/JAD-2011-102112
关键词
1,2-dioleoyl-3-trimethylammonium-propane; DOTAP; 1,2-dioleoyl-sn-glycero-3-phosphocholine DOPC; 1,2-dipalmitoyl-sn-glycero-3-phosphocholine; DPPC; 1,2-dioleoyl-sn-glycero-3-phospho-(1 '-rac-glycerol); DOPG; Alzheimer's disease; amyloid-beta(1-42); amyloid fibril formation; amyloid-lipid interactions; atomic force microscopy
资金
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Canada Foundation for Innovation (CFI)
- Ontario Ministry of Research and Innovation
Amyloid fibril formation is generally associated with many neurodegenerative disorders, including Alzheimer's disease (AD). Although fibril plaque formation is associated with biological membranes in vivo, the role of the cell surfaces in amyloid fibril formation and the molecular mechanism of amyloid toxicity are not well understood. Understanding the details of amyloid interaction with lipid membrane may shed light on the mechanism of amyloid toxicity. Using atomic force microscopy, we investigated aggregation of amyloid-beta(1-42) (A beta(1-42)) on model phospholipid membranes as a function of time and membrane composition. Neutral, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), anionic - 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DOPG), and cationic - 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), were used to study the effect of lipid type on amyloid binding. We show that both the charge on the lipid head group and lipid phase affect the interaction of amyloid oligomers with the membrane surface changing the rate of adsorption and causing changes in membrane structure and structure of amyloid deposits. We observed that amyloid aggregates progressively accumulate in a similar manner on the surface of neutral DPPC gel phase membrane and on the surface of fluid phase negatively charged DOPG membrane. In contrast to DPPC and DOPG, positively charged fluid DOTAP membrane and neutral fluid phase DOPC membrane contain amyloid deposits with reduced height, which suggests fusing of A beta(1-42) into the lipid membrane surface.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据