Membrane fusion and vesicular transformation induced by Alzheimer's amyloid beta.
Amyloid beta (Aβ) peptides, produced through endo-proteolytic cleavage of amyloid precursor protein, are thought to be involved in the death of neural cells in Alzheimer's disease (AD). Although the mechanisms are not fully known, it has been suggested that disruption of cellular activity due to Aβ interactions with the cell membrane may be one of the underlying causes. Here in, we have investigated the interaction between Aβ-42 and biomimetic lipid membranes and the resulting perturbations in the lipid vesicles. We have shown that Aβ oligomeric species localized closer to the membrane surface. Localization of the fibrillar species of Aβ-42, although varied, was not as closely associated with the membrane surface. We have demonstrated that the presence of Aβ-42 leads to an increase in membrane surface area, inducing lipid temporal vesicular transformation. Furthermore, we have unequivocally shown that Aβ-peptides mediate membrane fusion. Although membrane fusion induced by Aβ has been hypothesized/proposed, this is the first time it has been visually captured. This fusion may be one of the mechanisms behind the membrane increase in surface area and the resulting vesicular transformation. We have shown that the longer 'amyloidogenic' isoform causes vesicular transformation more readily, and has a higher membrane fusogenic potential than Aβ-40. Although not core to this study, it is hugely interesting to observe the high agreement between membrane dynamics and the reported amyloidogenicity of the peptides and aggregation species opening up the potential role of vesicular dynamics for profiling and biosensing of Aβ-induced neuro-toxicity.
School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi City, Ishikawa 923-1292, Japan.
Mun'delanji C
MC
Vestergaard
Masamune
M
Morita
Tsutomu
T
Hamada
Masahiro
M
Takagi
D016229:Amyloid beta-Peptides / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry*; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000737:chemistry; D010446:Peptide Fragments / Q000502:physiology*
D016229:Amyloid beta-Peptides; D008563:Membrane Lipids; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)