Insights into Mechanism of Aβ42 Fibril Growth on Surface of Graphene Oxides: Oxidative Degree Matters.

Abstract

The filamentous β-amyloid deposition has been regarded as the hallmark pathology of Alzheimer's disease (AD). Nanomaterials such as graphene oxides (GOs) have achieved significant progress in the therapy of AD, but the molecular pathway of the growth propagation remains challenging to investigate, especially on the surfaces of materials. The thermodynamics and kinetics of fibril elongation on GO surfaces with different oxidative degrees have been investigated by a combination of in vitro experiments and simulations. ThT kinetics, calorimetric measurements, and TEM observations suggest that low oxidative GO-10 promotes the fibril elongation, while both high oxidative GO-20 and GO-40 inhibit the fibril elongation. Computational results reveal that the apparent regulation behaviors of GOs on filament growth depend on the balance between the promoting effect by templating the incoming of monomers and the retarding effect by capturing the monomer during docking and locking phases through hydrogen bonding. This work will promote the understanding of the interplay between biomolecules and materials, thus providing new thoughts for the rational design of novel materials for amyloidosis therapy.

• Authors: Huan He, Juan Xu, Chen-Qiao Li, Tian Gao, Peng Jiang, Feng-Lei Jiang, Yi Liu
• Journal: Advanced healthcare materials (Adv Healthc Mater) Vol. 10 Issue 16 Pg. e2100436 (08 2021) ISSN: 2192-2659 [Electronic] Germany
• PMID: 34050633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Amyloid beta-Peptides
• Oxides
• Peptide Fragments
• Graphite

Topics

• Amyloid beta-Peptides (metabolism)
• Graphite
• Humans
• Molecular Dynamics Simulation
• Oxidative Stress
• Oxides
• Peptide Fragments