Alzheimer's disease amyloid-beta peptide analogue alters the ps-dynamics of phospholipid membranes.
We have investigated the influence of the neurotoxic Alzheimer's disease peptide amyloid-beta (25-35) on the dynamics of phospholipid membranes by means of quasi-elastic neutron scattering in the picosecond time-scale. Samples of pure phospholipids (DMPC/DMPS) and samples with amyloid-beta (25-35) peptide included have been compared. With two different orientations of the samples the directional dependence of the dynamics was probed. The sample temperature was varied between 290K and 320K to cover both the gel phase and the liquid-crystalline phase of the lipid membranes. The model for describing the dynamics combines a long-range translational diffusion of the lipid molecules and a spatially restricted diffusive motion. Amyloid-beta (25-35) peptide affects significantly the ps-dynamics of oriented lipid membranes in different ways. It accelerates the lateral diffusion especially in the liquid-crystalline phase. This is very important for all kinds of protein-protein interactions which are enabled and strongly influenced by the lateral diffusion such as signal and energy transducing cascades. Amyloid-beta (25-35) peptide also increases the local lipid mobility as probed by variations of the vibrational motions with a larger effect in the out-of-plane direction. Thus, the insertion of amyloid-beta (25-35) peptide changes not only the structure of phospholipid membranes as previously demonstrated by us employing neutron diffraction (disordering effect on the mosaicity of the lipid bilayer system) but also the dynamics inside the membranes. The amyloid-beta (25-35) peptide induced membrane alteration even at only 3mol% might be involved in the pathology of Alzheimer's disease as well as be a clue in early diagnosis and therapy.
Buchsteiner
Alexandra
A
Helmholtz-Zentrum Berlin für Materialien und Energie, Hahn-Meitner-Platz 1, D-14109 Berlin, Germany. buchsteiner@helmholtz-berlin.de
Hauss
Thomas
T
Dante
Silvia
S
Dencher
Norbert A
NA
D000465:Algorithms; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D033363:Neutron Diffraction / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013696:Temperature; D013997:Time Factors; D014494:Unithiol / Q000737:chemistry / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010743:Phospholipids; D014494:Unithiol; D004134:Dimyristoylphosphatidylcholine