Evaluating Effect of Metallic Ions On Aggregation Behavior of Amyloid Aβ42 By AFM Imaging and SERS

Abstract Background: Excessive aggregation of β-amyloid peptides (Aβ) is regarded as the hallmark of Alzheimer’s disease. Exploring the underlying mechanism regulating Aβ aggregation remains challenging and investigating aggregation events of Aβ in the presence and absence of metal ions at molecular level would be meaningful in elucidating the role of metal cations on interactions between Aβ molecules. In this study, chemical self-assembled monolayer (SAM) method was employed to fabricate monolayer of β-amyloid peptides Aβ42 on gold substrate with a bolaamphiphile named 16-Mercaptohexadecanoic acid (MHA). Firstly, the samples of gold substrate (blank control), the MHA-modified substrate and the Aβ42-modified substrate were detected by X-ray photoelectron spectroscopy (XPS) to track the self-assembly process. Aggregation behaviors of Aβ42 before and after metallic ions (Zn2+、Ca2+、Al3+) treated were monitored by atomic force microscopy (AFM) and the interaction between Aβ42 and metallic ions (Zn2+、Ca2+、Al3+) was investigated by surface-enhanced Raman Scattering (SERS), respectively.Results: The XPS spectra of binding energy of gold substrate (blank control), the MHA-modified substrate and the Aβ42-modified substrate are well fitted with the corresponding monolayer’s composition, which indicates that Aβ42 monolayer is well formed. The recorded surface morphology of different experimental groups obtained by AFM showed markedly different nanostructures, indicating occurrence of aggregation events between Aβ42 molecules after adding metal ions to the solution. Compared to the control group, the presence of metal ions resulted in the increased size of surface structures on the observed 3D topography. Further study by SERS showed that the Raman strength of Aβ42 changes significantly after the metal cation treatment. A considerable part of the amide bonds interacts with metal cations, leading to a structural change, which is characterized by the weakened β-fold Raman peak.Conclusion: The AFM imaging results suggest that aggregation events occurred between Aβ42 molecules with the addition of metal cations. Furthermore, the effect of metallic cations on the conformational change of Aβ42 studied by SERS supported the results obtained by AFM imaging. Taken together, the results showed that the presence of substoichiometric metal cations promotes aggregation behavior between Aβ42 molecules on the substrate at pH 7.4.

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Evaluating effect of metallic ions on aggregation behavior of β-amyloid peptides by atomic force microscope and surface-enhanced Raman Scattering

BioMedical Engineering OnLine ◽

10.1186/s12938-021-00972-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yang Xie ◽

Lin Yu ◽

Yuna Fu ◽

Heng Sun ◽

Jianhua Wang

Keyword(s):

Metal Cations ◽

Aggregation Behavior ◽

Metallic Ions ◽

Gold Substrate ◽

Amyloid Peptides ◽

Atomic Force ◽

Surface Enhanced ◽

Surface Enhanced Raman ◽

Enhanced Raman Scattering ◽

Β Amyloid

Abstract Background Excessive aggregation of β-amyloid peptides (Aβ) is regarded as the hallmark of Alzheimer’s disease. Exploring the underlying mechanism regulating Aβ aggregation remains challenging and investigating aggregation events of Aβ in the presence and absence of metallic ions at molecular level would be meaningful in elucidating the role of metal cations on interactions between Aβ molecules. In this study, chemical self-assembled monolayer (SAM) method was employed to fabricate monolayer of β-amyloid peptides Aβ42 on gold substrate with a bolaamphiphile named 16-Mercaptohexadecanoic acid (MHA). Firstly, the samples of gold substrate (blank control), the MHA-modified substrate, and the Aβ42-modified substrate were detected by X-ray photoelectron spectroscopy (XPS) to track the self-assembly process. Aggregation behaviors of Aβ42 before and after metallic ions (Zn2+, Ca2+, Al3+) treatment were monitored by atomic force microscopy (AFM) and the interaction between Aβ42 and metallic ions (Zn2+, Ca2+, Al3+) was investigated by surface-enhanced Raman Scattering (SERS). Results The XPS spectra of binding energy of gold substrate (blank control), the MHA-modified substrate, and the Aβ42-modified substrate are well fitted with the corresponding monolayer’s composition, which indicates that Aβ42 monolayer is well formed. The recorded surface morphology of different experimental groups obtained by AFM showed markedly different nanostructures, indicating occurrence of aggregation events between Aβ42 molecules after adding metal ions to the solution. Compared to the control group, the presence of metallic ions resulted in the increased size of surface structures on the observed 3D topography. Besides, the intermolecular rupture force of Aβ42 increased with the addition of metallic ions. Further study by SERS showed that the Raman strength of Aβ42 changes significantly after the metal cation treatment. A considerable part of the amide bonds interacts with metal cations, leading to a structural change, which is characterized by the weakened β-fold Raman peak. Conclusion The AFM imaging results suggest that aggregation events occurred between Aβ42 molecules with the addition of metal cations. In addition, the results of force tests indicate that the presence of metallic ions could promote adhesion between Aβ42 molecules, which is likely to be the trigger for aggregation behavior of Aβ42. Furthermore, the effect of metallic cations on the conformational change of Aβ42 studied by SERS supported the results obtained by AFM. Taken together, the results showed that the presence of substoichiometric metal cations promotes aggregation behavior between Aβ42 molecules on the substrate at pH 7.4.

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Evaluating Effect of Metallic Ions on Aggregation Behavior of Amyloid Aβ42 by AFM Imaging and SERS

10.21203/rs.3.rs-789688/v1 ◽

2021 ◽

Author(s):

Yang Xie ◽

Lin Yu ◽

Yuna Fu ◽

Heng Sun ◽

Chundong Liu ◽

...

Keyword(s):

Photoelectron Spectroscopy ◽

Self Assembly ◽

Metal Cations ◽

Aggregation Behavior ◽

Metallic Ions ◽

Gold Substrate ◽

Self Assembled Monolayer ◽

Afm Imaging ◽

Surface Enhanced Raman ◽

Aggregation Behaviors

Abstract In this study, self-assembled monolayer (SAM) method was employed to fabricate monolayer of β-amyloid peptides Aβ42 on gold substrate with a bolaamphiphile named thiol (MHA). Firstly, the samples of gold substrate (blank control), the MHA-modified substrate and the Aβ42-modified substrate were detected by X-ray photoelectron spectroscopy (XPS) to track the self-assembly process. The spectra of binding energy measured from these three sample surfaces could be well fitted with the corresponding monolayer’s composition, which means Aβ42 monolayer is well formed. Aggregation behaviors of Aβ42 in the absence and presence of metallic ions (Zn2+、Ca2+、Al3+) were then monitored by atomic force microscopy (AFM) and surface-enhanced Raman Scattering (SERS), respectively. The recorded surface morphology of different experimental groups obtained by AFM showed markedly different nanostructures, indicating occurrence of aggregation behaviors of Aβ42. In solutions with added metal ions, the increased size of surface structures was observed, which suggest the presence of metal cations promotes aggregation behavior between Aβ42 molecules. Furtherly, the interaction between Aβ42 and metal cations was investigated by SERS. The results demonstrate that the Raman strength of Aβ42 changes after the metal cation treatment. Taken together, the combined AFM imaging and Raman analyses show that the three kinds of metallic ions promote the process of Aβ42 aggregation.

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Melatonin prevents free radical formation due to the interaction between β -amyloid peptides and metal ions [Al(III), Zn(II), Cu(II), Mn(II), Fe(II)]

Journal of Pineal Research ◽

10.1034/j.1600-079x.2003.00058.x ◽

2003 ◽

Vol 35 (2) ◽

pp. 98-103 ◽

Cited By ~ 37

Author(s):

Paolo Zatta ◽

Giuseppe Tognon ◽

Paolo Carampin

Keyword(s):

Free Radical ◽

Metal Ions ◽

Radical Formation ◽

Amyloid Peptides ◽

Free Radical Formation ◽

Β Amyloid

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A kinetic study on the aggregation behavior of β-amyloid peptides in different initial solvent environments

Biochemical Engineering Journal ◽

10.1016/j.bej.2005.02.037 ◽

2006 ◽

Vol 29 (1-2) ◽

pp. 129-138 ◽

Cited By ~ 16

Author(s):

Steven S.-S. Wang ◽

Ya-Ting Chen ◽

Po-Han Chen ◽

Kuan-Nan Liu

Keyword(s):

Kinetic Study ◽

Aggregation Behavior ◽

Amyloid Peptides ◽

Β Amyloid

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Amentoflavone: A Bifunctional Metal Chelator that Controls the Formation of Neurotoxic Soluble Aβ42 Oligomers

10.26434/chemrxiv.12445505 ◽

2020 ◽

Author(s):

Liang Sun ◽

Anuj K. Sharma ◽

Byung-Hee Han ◽

Liviu M. Mirica

Keyword(s):

Reactive Oxygen Species ◽

Metal Ions ◽

Antioxidant Properties ◽

Reactive Oxygen ◽

Amyloid Plaques ◽

Transition Metal Ions ◽

Oxygen Species ◽

High Affinity ◽

Amyloid Aβ ◽

Β Amyloid

Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet the cause and progression of this disorder are not completely understood. While the main hallmark of AD is the deposition of amyloid plaques consisting of the β-amyloid (Aβ) peptide, transition metal ions are also known to play a significant role in disease pathology by expediting the formation of neurotoxic soluble β-amyloid (Aβ) oligomers, reactive oxygen species (ROS), and oxidative stress. Thus, bifunctional metal chelators that can control these deleterious properties are highly desirable. Herein, we show that amentoflavone (AMF) – a natural biflavonoid compound, exhibits good metal-chelating properties, especially for chelating Cu2+ with very high affinity (pCu7.4 = 10.44). In addition, AMF binds to Aβ fibrils with a high affinity (Ki = 287 ± 20 nM) – as revealed by a competition thioflavin T (ThT) assay, and specifically labels the amyloid plaques ex vivo in the brain sections of transgenic AD mice – as confirmed via immunostaining with an Ab antibody. The effect of AMF on Aβ42 aggregation and disaggregation of Aβ42 fibrils was also investigated, to reveal that AMF can control the formation of neurotoxic soluble Aβ42 oligomers, both in absence and presence of metal ions, and as confirmed via cell toxicity studies. Furthermore, an ascorbate consumption assay shows that AMF exhibits potent antioxidant properties and can chelate Cu2+ and significantly diminish the Cu2+-ascorbate redox cycling and reactive oxygen species (ROS) formation. Overall, these studies strongly suggest that AMF acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity, can also bind Cu2+ and mediate its deleterious redox properties, and thus AMF has the potential to be a lead compound for further therapeutic agent development for AD.

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