Induced β-Barrel Formation of the Alzheimer's Aβ25–35 Oligomers on Carbon Nanotube Surfaces: Implication for Amyloid Fibril Inhibition

Recent experimental studies show that carbon nanotubes impact the aggregation process of proteins associated with neurodegenerative diseases. However, the details of molecular interactions between proteins and carbon nanotubes are still not well understood. In this study, we investigate the initial adsorption features and dynamics of the Alzheimer's amyloid-β peptide spanning residues 25–35 (Aβ25–35) on a single-walled carbon nanotube (SWNT) surface using fully atomic molecular dynamics simulations (MD) in explicit solvent. The initial configurations of the Aβ25–35 peptides consist of two preformed bilayer β-sheets, each with four or five β-strands in parallel or mixed antiparallel-parallel orientations. Our simulations show, for what we believe is the first time, that two disjointed Aβ25–35 β-sheets with mixed antiparallel-parallel strands can assemble into β-barrels wrapping the SWNT. In contrast, both simulations of Aβ25–35 without SWNT, and simulations of SWNT−Aβ25–35 with purely parallel β-strands, lead to disordered aggregates. We find that Aβ25–35 β-barrel formation involves at least two steps: i), curving of the Aβ25–35 β-sheets as a result of strong hydrophobic interactions with carbon nanotube concomitantly with dehydration of the SWNT-peptide interface; and ii), intersheet backbone hydrogen bond formation with fluctuating intrasheet hydrogen bonds. Detailed analysis of the conversion shows that β-barrel formation on SWNT surface results from the interplay of dehydration and peptide-SWNT/peptide-peptide interactions. Implications of our results on amyloid fibril inhibition are discussed.