title: Effects of hydroxylated carbon nanotubes on the aggregation of Aβ16-22 peptides: a combined simulation and experimental study.
abstract: The pathogenesis of Alzheimer's disease (AD) is associated with the aggregation of amyloid-β (Aβ) peptides into toxic aggregates with ?-sheet character. In a previous computational study, we showed that pristine single-walled carbon nanotubes (SWCNTs) can inhibit the formation of β-sheet-rich oligomers in the central hydrophobic core fragment of Aβ (Aβ16-22). However, the poor solubility of SWCNTs in water hinders their use in biomedical applications and nanomedicine. Here, we investigate the influence of hydroxylated SWCNT, a water-soluble SWCNT derivative, on the aggregation of Aβ16-22 peptides using all-atom explicit-water replica exchange molecular dynamics simulations. Our results show that hydroxylated SWCNTs can significantly inhibit β-sheet formation and shift the conformations of Aβ16-22 oligomers from ordered β-sheet-rich structures toward disordered coil aggregates. Detailed analyses of the SWCNT-Aβ interaction reveal that the inhibition of β-sheet formation by hydroxylated SWCNTs mainly results from strong electrostatic interactions between the hydroxyl groups of SWCNTs and the positively charged residue K16 of Aβ16-22 and hydrophobic and aromatic stacking interactions between SWCNTs and F19 and F20. In addition, our atomic force microscopy and thioflavin T fluorescence experiments confirm the inhibitory effect of both pristine and hydroxylated SWCNTs on Aβ16-22 fibrillization, in support of our previous and present replica exchange molecular dynamics simulation results. These results demonstrate that hydroxylated SWCNTs efficiently inhibit the aggregation of Aβ16-22; in addition, they offer molecular insight into the inhibition mechanism, thus providing new clues for the design of therapeutic drugs against amyloidosis.
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai, China.
authors.forename: Luogang
authors.initials: L
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Mathematics and Physics, Shanghai University of Electric Power, Shanghai, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai, China.
authors.forename: Xinju
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai, China. Electronic address: ghwei@fudan.edu.cn.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wei
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006900:Hydroxylation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D066263:Protein Aggregation, Pathological; D055672:Static Electricity
chemical_list: D016229:Amyloid beta-Peptides; D037742:Nanotubes, Carbon; D010446:Peptide Fragments; C417223:amyloid beta-protein (16-22)