Ultrasmall Molybdenum Disulfide Quantum Dots Cage Alzheimer's Amyloid Beta to Restore Membrane Fluidity.

Abstract

Alzheimer's disease (AD) is a major cause of dementia characterized by the overexpression of transmembrane amyloid precursor protein and its neurotoxic byproduct amyloid beta (Aβ). A small peptide of considerable hydrophobicity, Aβ is aggregation prone catalyzed by the presence of cell membranes, among other environmental factors. Accordingly, current AD mitigation strategies often aim at breaking down the Aβ-membrane communication, yet no data is available concerning the cohesive interplay of the three key entities of the cell membrane, Aβ, and its inhibitor. Using a lipophilic Laurdan dye and confocal fluorescence microscopy, we observed cell membrane perturbation and actin reorganization induced by Aβ oligomers but not by Aβ monomers or amyloid fibrils. We further revealed recovery of membrane fluidity by ultrasmall MoS2 quantum dots, also shown in this study as a potent inhibitor of Aβ amyloid aggregation. Using discrete molecular dynamics simulations, we uncovered the binding of MoS2 and Aβ monomers as mediated by hydrophilic interactions between the quantum dots and the peptide N-terminus. In contrast, Aβ oligomers and fibrils were surface-coated by the ultrasmall quantum dots in distinct testudo-like, reverse protein-corona formations to prevent their further association with the cell membrane and adverse effects downstream. This study offers a crucial new insight and a viable strategy for regulating the amyloid aggregation and membrane-axis of AD pathology with multifunctional nanomedicine.

• Authors: Yuhuan Li, Huayuan Tang, Houjuan Zhu, Aleksandr Kakinen, Di Wang, Nicholas Andrikopoulos, Yunxiang Sun, Aparna Nandakumar, Eunbi Kwak, Thomas P Davis, David Tai Leong, Feng Ding, Pu Chun Ke
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 13 Issue 25 Pg. 29936-29948 (Jun 30 2021) ISSN: 1944-8252 [Electronic] United States
• PMID: 34143617 (Publication Type: Journal Article)

Chemical References

• Actins
• Amyloid beta-Peptides
• Disulfides
• Laurates
• Molybdenum
• 2-Naphthylamine
• laurdan
• molybdenum disulfide

Topics

• 2-Naphthylamine (analogs & derivatives, chemistry)
• Actins (chemistry, metabolism)
• Alzheimer Disease
• Amyloid beta-Peptides (chemistry, metabolism)
• Cell Line, Tumor
• Cell Membrane (chemistry, metabolism)
• Disulfides (chemistry)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Laurates (chemistry)
• Membrane Fluidity (physiology)
• Microscopy, Confocal
• Molecular Dynamics Simulation
• Molybdenum (chemistry)
• Nanomedicine
• Quantum Dots (chemistry)