Membrane-mimetic systems for biophysical studies of the amyloid-β peptide

Österlund, Nicklas; Luo, Jinghui; Wärmländer, Sebastian K.T.S.; Gräslund, Astrid

doi:10.1016/j.bbapap.2018.11.005

Cited by 38 publications

(52 citation statements)

References 100 publications

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“…An amyloid fibril is shown in blue (pdb 2MXU). d The hydrophobic C-terminal segment of Aβ is known to bind to phospholipid membranes [8], where an α-helical structure may be induced at low peptide concentrations [47]. Aβ is considered to oligomerize in the membrane environment, and this process may be affected by the specific membrane composition.…”

Section: Discussionmentioning

confidence: 99%

“…It is very challenging to mimic the complex and dynamic features of a living membrane in vitro or in silico, including regulation of the lipid phase and membrane asymmetry. Thus, model membranes with reduced complexity are often used in biophysical and molecular studies [8]. Most of the studies on interactions with metal ions and model membranes have been carried out for monomeric Aβ, but oligomeric aggregates likely have similar (although perhaps not identical) interactions.…”

Section: The Amyloid-β Peptides and Alzheimer's Diseasementioning

confidence: 99%

“…Interactions between Aβ peptides and membranes, by various mechanisms, have been suggested to be important for AD pathology [45,46]. Interactions with membrane models typically induce changes in the Aβ secondary structure, as demonstrated with, e.g., large unilamellar vesicles (LUVs), bicelles, planar lipid membranes, and micelles of detergents such as SDS [8,[47][48][49][50]. The local Aβ concentration can increase when the peptides bind to a membrane, which might facilitate Aβ self-interactions on the membrane surface [9,10].…”

Section: Aβ Interactions With Membranes and Membrane Mimetica: Pores mentioning

confidence: 99%

“…In many molecular studies of Aβ aggregation, micelleforming surfactants/detergents have been used in otherwise aqueous solvents, to achieve a simple membrane-mimetic environment [8,52]. For example, in the presence of sodium dodecyl sulfate (SDS) micelles, the more hydrophobic parts of the peptide insert into the micelle as two α-helical regions 16-24 and 29-35, held together by the unstructured 25-28 loop [49].…”

Section: Aβ Interactions With Membranes and Membrane Mimetica: Pores mentioning

confidence: 99%

“…The two α-helices involve residues 15-24 and 29-35. The metalbinding site is represented by a top-ranked cluster representation from a molecular dynamics simulation of Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) in complex with Zn(II) [23]. Model building and equilibration of a 62-molecule SDS micelle in water was done with the Micelle Maker [80].…”

Section: Aβ Interactions With Membranes and Membrane Mimetica: Pores mentioning

confidence: 99%

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Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

et al. 2019

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The amyloid-β (Aβ) peptides are key molecules in Alzheimer's disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric Aβ aggregates are known to induce membrane perturbations and the structure of these oligomers-and their membrane-perturbing effects-can be modulated by metal ion binding. If the bound metal ions are redox active, as e.g., Cu and Fe ions are, they will generate harmful reactive oxygen species (ROS) just outside the membrane surface. Thus, the membrane damage incurred by toxic Aβ oligomers is likely aggravated when redox-active metal ions are present. The combined interactions between Aβ oligomers, metal ions, and biomembranes may be responsible for at least some of the neuronal death in AD patients.

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Section: Discussionmentioning

confidence: 99%

Section: The Amyloid-β Peptides and Alzheimer's Diseasementioning

confidence: 99%

Section: Aβ Interactions With Membranes and Membrane Mimetica: Pores mentioning

confidence: 99%

Section: Aβ Interactions With Membranes and Membrane Mimetica: Pores mentioning

confidence: 99%

Section: Aβ Interactions With Membranes and Membrane Mimetica: Pores mentioning

confidence: 99%

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Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

et al. 2019

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The Membrane Axis of Alzheimer's Nanomedicine

Tang

Andrikopoulos

et al. 2020

Advanced NanoBiomed Research

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Alzheimer's disease (AD) is a major neurological disorder impairing its carrier's cognitive function, memory, and lifespan. While the development of AD nanomedicine is still nascent, the field is evolving into a new scientific frontier driven by the diverse physicochemical properties and theranostic potential of nanomaterials and nanocomposites. Characteristic to the AD pathology is the deposition of amyloid plaques and tangles of amyloid beta (Aβ) and tau, whose aggregation kinetics may be curbed by nanoparticle inhibitors via sequence‐specific targeting or nonspecific interactions with the amyloidogenic proteins. As literature implicates cell membrane as a culprit in AD pathogenesis, herein, the membrane axis of AD nanomedicine is summarized and a new rationale that the field development may greatly benefit from harnessing our existing knowledge of Aβ‐membrane interaction, nanoparticle–membrane interaction, and Aβ–nanoparticle interaction is presented.

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Imaging Amyloid‐β Membrane Interactions: Ion‐Channel Pores and Lipid‐Bilayer Permeability in Alzheimer's Disease

Viles

2023

Angewandte Chemie

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The accumulation of the amyloid-β peptides (Aβ) is central to the development of Alzheimer's disease. The mechanism by which Aβ triggers a cascade of events that leads to dementia is a topic of intense investigation. Aβ selfassociates into a series of complex assemblies with different structural and biophysical properties. It is the interaction of these oligomeric, protofibril and fibrillar assemblies with lipid membranes, or with membrane receptors, that results in membrane permeability and loss of cellular homeostasis, a key event in Alzheimer's disease pathology. Aβ can have an array of impacts on lipid membranes, reports have included: a carpeting effect; a detergent effect; and Aβ ion-channel pore formation. Recent advances imaging these interactions are providing a clearer picture of Aβ induced membrane disruption. Understanding the relationship between different Aβ structures and membrane permeability will inform therapeutics targeting Aβ cytotoxicity.

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Membrane-mimetic systems for biophysical studies of the amyloid-β peptide

Cited by 38 publications

References 100 publications

Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

The Membrane Axis of Alzheimer's Nanomedicine

Imaging Amyloid‐β Membrane Interactions: Ion‐Channel Pores and Lipid‐Bilayer Permeability in Alzheimer's Disease

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