Carbon nanotube inhibits the formation of ?-sheet-rich oligomers of the Alzheimer's amyloid-?(16-22) peptide.

ABSTRACT: Alzheimer's disease is associated with the abnormal self-assembly of the amyloid-? (A?) peptide into toxic ?-rich aggregates. Experimental studies have shown that hydrophobic nanoparticles retard A? fibrillation by slowing down the nucleation process; however, the effects of nanoparticles on A? oligomeric structures remain elusive. In this study, we investigate the conformations of A?(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 A?(16-22) solution prevents ?-sheet formation. Simulation starting from a prefibrillar ?-sheet octamer shows that SWCNT destabilizes the ?-sheet structure. A detailed analysis of the A?(16-22)/SWCNT/water interactions reveals that both the inhibition of ?-sheet formation and the destabilization of prefibrillar ?-sheets by SWCNT result from the same physical forces: hydrophobic and ?-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 A?(16-22) and full-length A? fibrillation.

SUBMITTER: Li H 

PROVIDER: S-EPMC3207167 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature