Gold Nanoparticles as a Probe for Amyloid-β Oligomer and Amyloid Formation

Elbassal, Esmail A.; Morris, Clifford; Kent, Thomas W.; Lantz, Richard; Ojha, Bimlesh; Wojcikiewicz, Ewa P.; Du, Deguo

doi:10.1021/acs.jpcc.7b05169

Cited by 51 publications

(38 citation statements)

References 63 publications

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“…They have become a very useful tool in immunoassay and nucleic acid analysis and have been widely applied in food safety, environmental protection and clinical laboratories. [15][16][17] However, methods to detect AuNPs or AuNP-labelled substances are limited to colorimetric, photometric, electron microscopy, and photomicrography with the help of visual methods. This results in difficulties in the accurate determination of AuNPs or AuNP-labelled substances.…”

Section: Introductionmentioning

confidence: 99%

Electrochemiluminescence of gold nanoparticles and gold nanoparticle-labelled antibodies as co-reactants

et al. 2018

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Section: Introductionmentioning

confidence: 99%

Electrochemiluminescence of gold nanoparticles and gold nanoparticle-labelled antibodies as co-reactants

et al. 2018

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“…In addition, it was found that large AuNPs accelerate Aβ fibrillation, whereas small AuNPs significantly suppress the inhibition process. Esmail et al have used AuNPs to detect the formation of Aβ amyloid fibrils and oligomers 24 . They have demonstrated that the surface plasmon resonance (SPR) band intensity of the AuNPs is sensitive to the presence of oligomers of both Aβ40 and an Aβ40 mutant.…”

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confidence: 99%

Biopolymer-coated gold nanoparticles inhibit human insulin amyloid fibrillation

Meesaragandla

Karanth

Janke

et al. 2020

Sci Rep

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Deposits of protein misfolding and/or aggregates are a pathological hallmark of amyloid-related diseases. For instance, insulin amyloid fibril deposits have been observed in patients with insulindependent diabetes mellitus after insulin administration. Here, we report on the use of AuNPs functionalized with linear-(i.e. dextrin and chitosan) and branched-(i.e. dextran-40 and dextran-10) biopolymers as potential agents to inhibit insulin fibril formation. Our dynamic light scattering analyses showed a size decrease of the amyloid fibrils in the presence of functionalized AuNPs. Circular dichroism spectroscopy as well as enzyme-linked immunosorbent assay data demonstrated that the secondary structural transition from α-helix to β-sheet (which is characteristic for insulin amyloid fibril formation) was significantly suppressed by all biopolymer-coated AuNPs, and in particular, by those functionalized with linear biopolymers. Both transmission electron microscopy and atomic force microscopy analyses showed that the long thick amyloid fibrils formed by insulin alone become shorter, thinner or cluster when incubated with biopolymer-coated AuNPs. Dextrin-and chitosan-coated AuNPs were found to be the best inhibitors of the fibril formation. Based on these results, we propose a mechanism for the inhibition of insulin amyloid fibrils: biopolymer-coated AuNPsstrongly interact with the insulin monomers and inhibit the oligomer formation as well as elongation of the protofibrils.Moreover, cytotoxicity experiments showed that AuNP-insulin amyloid fibrils are less toxic compared to insulin amyloid fibrils alone. Our results suggest that both dextrin-and chitosan-AuNPs could be used as therapeutic agents for the treatment of amyloid-related disorders. Deposition of insoluble protein aggregates referred as amyloids has been observed as a common feature of various degenerative diseases (e.g. Alzheimer's, type II diabetes, Parkinson's, and Huntington's disease) 1-5. Almost 20 different human proteins have been identified to form amyloid deposits and aggregates in intracellular and extracellular matrix of the brain 6. Amyloid fibrils have been recognized as highly-ordered aggregates, rich in cross β-sheet secondary structures with unbranched filamentous morphology 7. Generally, amyloid fibril formation involves several steps including oligomers, protofibrils, and fibrils 8,9. Each of these forms has distinctive molecular conformations and different degrees of toxicity to the neuronal cells 10. One of the human proteins where amyloid fibril formation is considered a major problem is insulin. It is a 51-residue polypeptide hormone involved in regulating the blood glucose level and is used for the treatment of diabetes. It consists of an A-chain (21-residues) and B-chain (30-residues) which are connected by a pair of inter-chain disulfide bonds 11. Furthermore, it has been shown to exhibit an in vitro amyloid fibril-forming tendency at certain destabilizing conditions (e.g., low pH, elevated temperature, increased ionic strength, and ...

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“…These are consistent with our previous report that the aggregation of this peptide produces stable oligomers instead of proceeding to form fibrils in phosphate buffer. [8] The Lys16 residue is in close proximity to the hydrophobic core “L 17 VFFA 21 ” region, which is essential for Aβ oligomer and fibril formation. [9] K16Nle mutagenesis dramatically increases the hydrophobicity of the peptide (Table S1).…”

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confidence: 99%

N‐Terminal Charged Residues of Amyloid‐β Peptide Modulate Amyloidogenesis and Interaction with Lipid Membrane

Morris

Cupples

Kent

et al. 2018

Chemistry A European J

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Interactions of amyloid-β (Aβ) peptides and cellular membranes are proposed to be closely related with Aβ neurotoxicity in Alzheimer’s disease. In this study, we systematically investigated the effect of the N-terminal hydrophilic region of Aβ40 on its amyloidogenesis and interaction with supported phospholipid bilayer. Our results show that modulation of the charge properties of the dynamic N-terminal region dramatically influences the aggregation properties of Aβ. Furthermore, our results demonstrate that the N-terminal charged residues play a crucial role in driving the early adsorption and latter remobilization of the peptide on membrane bilayer, and mediating the rigidity and viscoelasticity properties of the bound Aβ40 at the membrane interface. The results provide new mechanistic insight into the early Aβ-membrane interactions and binding, which may be critical for elucidating membrane-mediated Aβ amyloidogenesis in a physiological environment and unravelling the origin of Aβ neurotoxicity.

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Gold Nanoparticles as a Probe for Amyloid-β Oligomer and Amyloid Formation

Cited by 51 publications

References 63 publications

Electrochemiluminescence of gold nanoparticles and gold nanoparticle-labelled antibodies as co-reactants

Electrochemiluminescence of gold nanoparticles and gold nanoparticle-labelled antibodies as co-reactants

Biopolymer-coated gold nanoparticles inhibit human insulin amyloid fibrillation

N‐Terminal Charged Residues of Amyloid‐β Peptide Modulate Amyloidogenesis and Interaction with Lipid Membrane

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