Mechanistic insights into the size-dependent effects of nanoparticles on inhibiting and accelerating amyloid fibril formation

John, Torsten; Adler, Juliane; Elsner, Christian; Petzold, Johannes; Krueger, Martin; Martin, L.; Huster, Daniel; Risselada, Herre Jelger; Abel, Bernd

doi:10.1016/j.jcis.2022.04.134

Cited by 27 publications

(37 citation statements)

References 116 publications

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“…Liposomes and micelles present large surface-to-volume ratios in the nanometer size range (see SI Figure S2). 61,90,91 In the presence of strong electrostatic surface attraction, the absorption of peptides onto micelles and liposomes can inhibit the formation of amyloid fibrils by depleting the free concentration of monomers in solution thereby reducing peptide mobility and flexibility. In the presence of weak surface attraction, micelle and liposome surfaces may act as potential adsorption and nucleation points for peptides and can seed aggregation.…”

Section: Resultsmentioning

confidence: 99%

Lipid Oxidation Controls Peptide Self-Assembly near Membranes

John

Piantavigna

Dealey

et al. 2022

Preprint

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The self-assembly of peptides into supramolecular fibril structures has been linked to neurodegenerative diseases such as Alzheimer's disease but has also been observed in functional roles. Peptides are physiologically exposed to crowded environments of biomacromolecules, and particularly membrane lipids, within a cellular milieu. Previous research has shown that membranes can both accelerate and inhibit peptide self-assembly. Here, we studied the impact of biomimetic membranes that mimic cellular oxidative stress and compared this to mammalian and bacterial membranes. Using molecular dynamics simulations and experiments, we propose a model that explains how changes in peptide-membrane binding, electrostatics, and peptide secondary structure stabilization determine the nature of peptide self-assembly. We explored the influence of zwitterionic (POPC), anionic (POPG) and oxidized (PazePC) phospholipids, as well as cholesterol, and mixtures thereof, on the self-assembly kinetics of the amyloid β (1–40) peptide (Aβ40), linked to Alzheimer's disease, and the amyloid-forming antimicrobial peptide uperin 3.5 (U3.5). We show that the presence of an oxidized lipid had similar effects on peptide self-assembly as the bacterial mimetic membrane. While Aβ40 fibril formation was accelerated, U3.5 aggregation was inhibited by the same lipids at the same peptide-to-lipid ratio. We attribute these findings and peptide-specific effects to differences in peptide-membrane adsorption with U3.5 being more strongly bound to the membrane surface and stabilized in an α-helical conformation compared to Aβ40. Different peptide-to-lipid ratios resulted in different effects. Molecular dynamics simulations provided detailed mechanistic insights into the peptide-lipid interactions and secondary structure stability. We found that electrostatic interactions are a primary driving force for peptide-membrane interaction, enabling us to propose a model for predictions how cellular changes might impact peptide self-assembly in vivo, and potentially impact related diseases.

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Section: Resultsmentioning

confidence: 99%

Lipid Oxidation Controls Peptide Self-Assembly near Membranes

John

Piantavigna

Dealey

et al. 2022

Preprint

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“…The development of the curvature model and the method for the molecular dynamics (MD) simulations were published in the related original research article [1] . Detailed practical information on using the data and setting up simulations can be found here.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…In addition, molecular dynamics (MD) simulation data is provided and detailed below. The interpretation of the data and results was published in the Journal of Colloid and Interface Science [1] . The curvature model uses a spherical harmonic potential to implicitly describe a nanoparticle of radius r 0 , while the attraction of the adsorbed oligomer is controlled by defining the potential force constant k (see Fig.…”

Section: Data Descriptionmentioning

confidence: 99%

“…The *.mdp and *.top files are useful for repeating or extending the simulations and can serve as a guide to create different simulations with our curvature model. We also provide a force field folder for the OPLA/AA force field that we used for the peptides in the related research article [1] and the data included here [13 , 14] . We note that any other force field can be used in combination with the curvature potential.…”

Section: Data Descriptionmentioning

confidence: 99%

“…This makes them highly relevant for biomolecules, such as peptides. In this data article, we present a curvature model and molecular dynamics (MD) simulation data on the influence of nanoparticle size on the stability of amyloid peptide fibrils related to our research article entitled “Mechanistic insights into the size-dependent effects of nanoparticles on inhibiting and accelerating amyloid fibril formation” (John et al., 2022) [1] . We provide the code to perform MD simulations in GROMACS 4.5.7 software of arbitrarily chosen biomolecule oligomers adsorbed on a curved surface of chosen nanoparticle size.…”

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confidence: 99%

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Curvature model for nanoparticle size effects on peptide fibril stability and molecular dynamics simulation data

et al. 2022

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The Design of Metal Complexes to Target the Amyloid‐β Peptide in Alzheimer's Disease

Webb

2023

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Alzheimer's disease (AD) is a devastating neurological disorder where a pathological hallmark is the occurrence of amyloid‐β (Aβ) peptide deposits, also known as Aβ plaques. The Aβ peptide is known to self‐associate and aggregate in solution, a phenomenon that is accelerated in the presence of metal ions, in particular Fe, Cu, and Zn. Furthermore, these micronutrient metals are found in elevated concentration within Aβ plaques, relative to nearby healthy tissues. Therapeutic approaches have sought to exploit this metalloprotein nature of Aβ by designing metal complexes that can target either the soluble peptide or its pathological aggregate species. Overall, complexes of 27 different metals have been designed to target the Aβ that can detect its presence in biological samples, modulate its aggregation, and/or prevent its neurotoxic activity. This article summarizes these compounds, and the advances made for complexes of each metal.

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Mechanistic insights into the size-dependent effects of nanoparticles on inhibiting and accelerating amyloid fibril formation

Cited by 27 publications

References 116 publications

Lipid Oxidation Controls Peptide Self-Assembly near Membranes

Lipid Oxidation Controls Peptide Self-Assembly near Membranes

Curvature model for nanoparticle size effects on peptide fibril stability and molecular dynamics simulation data

The Design of Metal Complexes to Target the Amyloid‐β Peptide in Alzheimer's Disease

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