title: Differing modes of interaction between monomeric Aβ(1-40) peptides and model lipid membranes: an AFM study.
abstract: Membrane interactions with β-amyloid peptides are implicated in the pathology of Alzheimer's disease and cholesterol has been shown to be key modulator of this interaction, yet little is known about the mechanism of this interaction. Using atomic force microscopy, we investigated the interaction of monomeric Aβ(1-40) peptides with planar mica-supported bilayers composed of DOPC and DPPC containing varying concentrations of cholesterol. We show that below the bilayer melting temperature, Aβ monomers adsorb to, and assemble on, the surface of DPPC bilayers to form layers that grow laterally and normal to the bilayer plane. Above the bilayer melting temperature, we observe protofibril formation. In contrast, in DOPC bilayers, Aβ monomers exhibit a detergent-like action, forming defects in the bilayer structure. The kinetics of both modes of interaction significantly increases with increasing membrane cholesterol content. We conclude that the mode and rate of the interaction of Aβ monomers with lipid bilayers are strongly dependent on lipid composition, phase state and cholesterol content.
authors.affiliation: Nanoscale Function Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland. khizar 001@yahoo.co.uk
authors.forename: Khizar
authors.initials: K
authors.lastname: Sheikh
authors.forename: Cristiano
authors.initials: C
authors.lastname: Giordani
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: McManus
authors.forename: Mads Bruun
authors.initials: MB
authors.lastname: Hovgaard
authors.forename: Suzanne P
authors.initials: SP
authors.lastname: Jarvis
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C078592:amyloid beta-protein (1-40); D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine