title: Amyloid-β aggregation on model lipid membranes: an atomic force microscopy study.
abstract: 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-β1-42 (Aβ1-42) 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 showed 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 Aβ1-42 into the lipid membrane surface.
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Hane
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Drolle
authors.forename: Ravi
authors.initials: R
authors.lastname: Gaikwad
authors.forename: Erin
authors.initials: E
authors.lastname: Faught
authors.forename: Zoya
authors.initials: Z
authors.lastname: Leonenko
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005782:Gels; D007091:Image Processing, Computer-Assisted; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000737:chemistry*; D008567:Membranes, Artificial; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012984:Software
chemical_list: D016229:Amyloid beta-Peptides; D005229:Fatty Acids, Monounsaturated; D005782:Gels; D008051:Lipid Bilayers; D008563:Membrane Lipids; D008567:Membranes, Artificial; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D000644:Quaternary Ammonium Compounds; C075222:amyloid beta-protein (1-42); D015060:1,2-Dipalmitoylphosphatidylcholine; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; C017251:1,2-oleoylphosphatidylcholine; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane