title: Carbon nanotube inhibits the formation of β-sheet-rich oligomers of the Alzheimer's amyloid-β(16-22) peptide.
abstract: Alzheimer's disease is associated with the abnormal self-assembly of the amyloid-β (Aβ) peptide into toxic β-rich aggregates. Experimental studies have shown that hydrophobic nanoparticles retard Aβ fibrillation by slowing down the nucleation process; however, the effects of nanoparticles on Aβ oligomeric structures remain elusive. In this study, we investigate the conformations of Aβ(16-22) octamers in the absence and presence of a single-walled carbon nanotube (SWCNT) by performing extensive all-atom replica exchange molecular-dynamics simulations in explicit solvent. Our simulations starting from eight random chains demonstrate that the addition of SWCNT into Aβ(16-22) solution prevents β-sheet formation. Simulation starting from a prefibrillar β-sheet octamer shows that SWCNT destabilizes the β-sheet structure. A detailed analysis of the Aβ(16-22)/SWCNT/water interactions reveals that both the inhibition of β-sheet formation and the destabilization of prefibrillar β-sheets by SWCNT result from the same physical forces: hydrophobic and π-stacking interactions (with the latter playing a more important role). By analyzing the stacking patterns between the Phe aromatic rings and the SWCNT carbon rings, we find that short ring-centroid distances mostly favor parallel orientation, whereas large distances allow all other orientations to be populated. Overall, our computational study provides evidence that SWCNT is likely to inhibit Aβ(16-22) and full-length Aβ fibrillation.
authors: State Key Laboratory of Surface Physics and Department of Physics, Fudan University, Shanghai, China.
authors: Huiyu
authors: H
authors: Li
authors: Yin
authors: Y
authors: Luo
authors: Philippe
authors: P
authors: Derreumaux
authors: Guanghong
authors: G
authors: Wei
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D037742:Nanotubes, Carbon / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D037742:Nanotubes, Carbon