Amyloid-beta Aggregation on Model Lipid Membranes: An Atomic Force Microscopy Study

作者：Hane Francis; Drolle Elizabeth; Gaikwad Ravi; Faught Erin; Leonenko Zoya^*

来源：Journal of Alzheimer's Disease, 2011, 26(3): 485-494.

DOI：10.3233/JAD-2011-102112

• 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

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.

• 出版日期2011