Carbon Nanotube Inhibits the Formation of β-Sheet-Rich Oligomers of the Alzheimer's Amyloid-β(16-22) Peptide

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