Impact of phospholipid bilayer saturation on amyloid-beta protein aggregation intermediate growth: a quartz crystal microbalance analysis.
Evidence that membrane-associated amyloid aggregate growth can impart membrane damage represents one possible mechanism for the neurodegeneration associated with deposited amyloid-beta protein (Abeta) aggregates in the brains of Alzheimer's disease (AD) patients. This potential pathogenic event necessitates an understanding of the impact that cellular membrane composition may have on Abeta aggregate growth. In the current study, a quartz crystal microbalance (QCM) was employed to examine the growth of Abeta(1-40) aggregation intermediates on supported phospholipid bilayers (SPBs) assembled at the crystal surface. These surface-specific measurements illustrate that zwitterionic SPBs selectively bind aggregated but not monomeric protein, and these bound aggregates are capable of supporting nonsaturable reversible growth via monomer addition. Growth-capable Abeta(1-40) aggregation intermediates more readily bind SPBs composed of phospholipids with a greater degree of carbon saturation. Furthermore, kinetic analysis afforded by the quantitative real-time QCM measurements reveals that SPBs with greater saturation also better support the growth of bound Abeta(1-40) aggregation intermediates as a result of the slower dissociation of bound monomer rather than more efficient recognition between aggregate and monomeric protein. These findings correlate with epidemiological and experimental evidence that links increased dietary intake of polyunsaturated fatty acids to a reduced risk of AD.
Kotarek
J A
JA
Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA.
Moss
M A
MA
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010655:Phenylenediamines / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011791:Quartz
D016229:Amyloid beta-Peptides; D005227:Fatty Acids; D008051:Lipid Bilayers; D008081:Liposomes; D010446:Peptide Fragments; D010655:Phenylenediamines; D010713:Phosphatidylcholines; D010743:Phospholipids; C078592:amyloid beta-protein (1-40); D011791:Quartz; C004845:N,N'-diphenyl-4-phenylenediamine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine