Influence of amyloid-β peptides with different lengths and amino acid sequences on the lateral diffusion of lipids in model membranes

Abstract

We have investigated the influence of two neurotoxic Alzheimer's disease peptide analogues with different lengths and amino acid compositions, amyloid-β(25–35) and amyloid-β(22–40), on the dynamics of phospholipid membranes by means of quasi-elastic neutron scattering in the picosecond time domain. Samples of pure phospholipids (DMPC/DMPS) and samples with embedded amyloid-β peptides have been compared. The peptide concentration was 3 mol% for both amyloid-β peptides. The sample temperature was set to 320 K, where the samples are in the liquid crystalline phase, which is the physiologically relevant phase of biological membranes. The data have been analyzed with a purely phenomenological model, which combines two different motions with different time constants. These two motions have been assigned to a long-range translational diffusion and a spatially restricted (localized) diffusion. The different lengths of the peptides leads to different positions and orientations inside the membrane bilayers. Thus, different influences on the dynamics are also expected. Both amyloid-β peptides significantly affected the ps-dynamics of oriented lipid membranes. Mainly, they accelerated the long-range translational diffusion even though the peptide concentration was quite low. This finding is of relevance for all kinds of protein–protein interactions, which are strongly influenced by the lateral diffusion, such as signal transduction cascades and energy transfer. This influence might be involved in the pathology of Alzheimer's disease as well as being a clue for early diagnosis and in therapy.