Lipid-induced beta-amyloid peptide assemblage fragmentation.
Alzheimer's disease is the most common cause of dementia and is widely believed to be due to the accumulation of beta-amyloid peptides (Abeta) and their interaction with the cell membrane. Abetas are hydrophobic peptides derived from the amyloid precursor proteins by proteolytic cleavage. After cleavage, these peptides are involved in a self-assembly-triggered conformational change. They are transformed into structures that bind to the cell membrane, causing cellular degeneration. However, it is not clear how these peptide assemblages disrupt the structural and functional integrity of the membrane. Membrane fluidity is one of the important parameters involved in pathophysiology of disease-affected cells. Probing the Abeta aggregate-lipid interactions will help us understand these processes with structural detail. Here we show that a fluid lipid monolayer develop immobile domains upon interaction with Abeta aggregates. Atomic force microscopy and transmission electron microscopy data indicate that peptide fibrils are fragmented into smaller nano-assemblages when interacting with the membrane lipids. Our findings could initiate reappraisal of the interactions between lipid assemblages and Abeta aggregates involved in Alzheimer's disease.
Widenbrant
Martin J O
MJ
Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
Rajadas
Jayakumar
J
Sutardja
Christopher
C
Fuller
Gerald G
GG
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004295:Dihydroxyphenylalanine / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008055:Lipids / Q000737:chemistry; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry; D011485:Protein Binding; D012212:Rheology
D016229:Amyloid beta-Peptides; D008055:Lipids; D010455:Peptides; D010715:Phosphatidylglycerols; D004295:Dihydroxyphenylalanine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol