Investigation of the Dissociation Mechanism of Single-Walled Carbon Nanotube on Mature Amyloid-β Fibrils at Single Nanotube Level

Abstract

Amyloid fibrils originating from the fibrillogenesis of misfolded amyloid proteins are associated with the pathogenesis of many neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's diseases. Carbon nanotubes have been extensively applied in our life and industry due to their unique chemical and physical properties. Nonetheless, the details between carbon nanotubes and mature amyloid fibrils remain elusive. In this study, we explored the interplay between single-walled carbon nanotubes (SWCNTs) and preformed amyloid-β (Aβ) fibrils by atomic force microscopy at the single SWCNT level, together with ThT fluorescence, cellular viability assays, infrared spectroscopy, and molecular dynamics (MD) simulations. The results demonstrated that SWCNTs could partially destroy the preformed Aβ fibrils and form the Aβ-surrounded− SWCNTs conjugates, as well as reduce the β-sheet structures. Peak force quantitative nanomechanical measurements revealed that the conjugates have lower Young's modulus than fibrils. Furthermore, our MD simulation demonstrated that the dissociation ability was dependent on the binding sites of Aβ fibrils. Overall, this study provides an insight into the dissociation mechanism between SWCNT and Aβ fibrils, which could be beneficial for the study of bionanomaterials and the development of other potential drug candidates for amyloidosis.

High Speed AFM and NanoInfrared Spectroscopy Investigation of Aβ1–42 Peptide Variants and Their Interaction With POPC/SM/Chol/GM1 Model Membranes

“…Shorter cross-over distances are also observed, but evolved with time, increasing from ∼40 nm at day 1 to ∼60 nm at day 7 and ∼70 nm at day 10 of incubation ( Figures 3H-J). At day 7 of incubation, twisted fibers are co-existing with non-twisted ones, though the later are a minority in our samples ( Figures 3A,B), and curved fibers are also present at day 10 in a low proportion ( Figure 3C), which is consistent with previously observed mature Aβ 1-42 WT fibers (Lin et al, 2020).…”

Turning the structure of the Aβ42peptide by different functionalized carbon nanotubes: a molecular dynamics simulation study

“…22 Lin et al investigated the dissociation mechanism between single-walled CNTs and mature amyloid fibers by experiments and molecular dynamics (MD) simulations. 23 Generally, there are many factors such as size, 24 shapes, 25 curvature, 26–28 effective hydrophobicity, 29 surface functionality, 30 and solubility 31 that affect the interactions between CNTs and proteins. In 2019, Zhang et al demonstrated that the structure of the Aβ 42 peptides can be significantly tuned by changing the curvature of CNTs.…”

Fullerenes as an Effective Amyloid Fibrils Disaggregating Nanomaterial

“…Second, although two different proteins and two fullerenes have been used, the DC 50 values were found to be quite similar, thus suggesting a common mechanism of fibrils disassembly regardless of fibrils formed by different proteins. Moreover, the DC 50 values obtained for studied fullerenes are lower in comparison with the DC 50 values reported previously for other types of nanosized materials, such as superparamagnetic iron oxide nanoparticles and cerium dioxide nanoparticles, and were calculated for insulin, lysozyme, alpha-lactalbumin, beta-lactoglobulin, Aβ-peptide, and others. − High potential to disassemble amyloid fibrils was reported also for gold and silver nanoparticles/nanorods, especially with coapplication of radiation. − Similar disassembly ability comparing to our study was observed for graphene oxide and carbon nanotubes. , It is important that low concentrations of NMP have very little impact on protein amyloid aggregates. The increasing NMP concentration up to 120 mg/mL (fullerene to protein (w/w) ratio 2:1) results in ∼20% decrease of ThT fluorescence, suggesting possible interaction of NMP with amyloid fibrils.…”

“…62−65 Similar disassembly ability comparing to our study was observed for graphene oxide and carbon nanotubes. 66,67 It is important that low concentrations of NMP have very little impact on protein amyloid aggregates. The increasing NMP concentration up to 120 mg/mL (fullerene to protein (w/w) ratio 2:1) results in ∼20% decrease of ThT fluorescence, suggesting possible interaction of NMP with amyloid fibrils.…”