Aggregation of amyloid-β (Aβ) peptides into prefibrillar toxic oligomers is responsible for Alzheimer’s disease, which is one of the most commonly known forms of neurodegenerative diseases. It has been reported that the low-molecular weight Aβ(1–42) trimer and its higher order oligomers are responsible for the cytotoxicity in the neuronal cells, leading to their death. Various experimental studies have shown that boron nitride nanotube (BNNTs) are noncytotoxic for health and environment and biocompatible in living cells and can be used as delivery vehicles for brain anticancer drugs. Here, we investigate the effects of BNNT on the secondary structure of Aβ(1–42) in the amyloid oligomerization process. We have performed long atomistic molecular dynamics simulations of 4.0 μs in total to study the structural stability of Aβ(1–42) trimer both in presence and absence of BNNT in explicit solvent. It is found that in the absence of BNNT, Aβ(1–42) trimer aggregates, leading to α-helix to β-sheet transition, whereas BNNT provides structural stability to the peptides by keeping them separated and preserving the initial monomeric helical conformation of the Aβ(1–42) trimer. It is found through a free-energy decomposition analysis that the key residues (Lys28, Ile31, Ile32, Leu34, Val40, and Ile41) from the C-terminal that are more responsible for β-sheet fibril formation bind with the BNNT surface and block their structural conversion. Due to the presence of polar B–N bonds, BNNT is less hydrophobic as compared with the carbonaceous nanomaterials where large hydrophobicity of these carbonaceous nanomaterials mostly destabilizes the secondary structure of peptides. The current study reveals that the less hydrophobicity of BNNT provides stability of the initial secondary structure of the Aβ(1–42) trimer and hinders their aggregation. Hence, the secondary structure stabilization in presence of BNNT provides new possibilities for the design of different nanoparticles as therapeutic agents for different types of amyloidogenesis by tuning their hydrophobicity.

The aggregation of amyloid β (Aβ) peptide triggered by its conformational changes leads to the commonly known neurodegenerative disease of Alzheimer's. It is believed that the formation of β sheets of the peptide plays a key role in its aggregation and subsequent fibrillization. In the current study, we have investigated the interactions of the Aβ(1−42) peptide with boron nitride nanoparticles and the effects of the latter on conformational transitions of the peptide through a series of molecular dynamics simulations. In particular, the effects of curvature of the nanoparticle surface are studied by considering boron nitride nanotubes (BNNTs) of varying diameter and also a planar boron nitride nanosheet (BNNS). Altogether, the current study involves the generation and analysis of 9.5 μs of dynamical trajectories of peptide-BNNT/BNNS pairs in an aqueous medium. It is found that BN nanoparticles of different curvatures that are studied in the present work inhibit the conformational transition of the peptide to its β-sheet form. However, such an inhibition effect follows different pathways for BN nanoparticles of different curvatures. For the BNNT with the highest surface curvature, i.e., (3,3) BNNT, the nanoparticle is found to inhibit β-sheet formation by stabilizing the helical structure of the peptide, whereas for planar BNNS, the β-sheet formation is prevented by making more favorable pathways available for transitions of the peptide to conformations of random coils and turns. The BNNTs with intermediate curvatures are found to exhibit diverse pathways of their interactions with the peptide, but in all cases, essentially no formation of the β sheet is found whereas substantial β-sheet formation is observed for Aβ(1−42) in water in the absence of any nanoparticle. The current study shows that BN nanoparticles have the potential to act as effective tools to prevent amyloid formation from Aβ peptides.