Amyloid-β Peptide Interactions with Amphiphilic Surfactants : Electrostatic and Hydrophobic Effects
(2018) In ACS Chemical Neuroscience 9(7). p.1680-1692- Abstract
The amphiphilic nature of the amyloid-β (Aβ) peptide associated with Alzheimer's disease facilitates various interactions with biomolecules such as lipids and proteins, with effects on both structure and toxicity of the peptide. Here, we investigate these peptide-amphiphile interactions by experimental and computational studies of Aβ(1-40) in the presence of surfactants with varying physicochemical properties. Our findings indicate that electrostatic peptide-surfactant interactions are required for coclustering and structure induction in the peptide and that the strength of the interaction depends on the surfactant net charge. Both aggregation-prone peptide-rich coclusters and stable surfactant-rich coclusters can form. Only Aβ(1-40)... (More)
The amphiphilic nature of the amyloid-β (Aβ) peptide associated with Alzheimer's disease facilitates various interactions with biomolecules such as lipids and proteins, with effects on both structure and toxicity of the peptide. Here, we investigate these peptide-amphiphile interactions by experimental and computational studies of Aβ(1-40) in the presence of surfactants with varying physicochemical properties. Our findings indicate that electrostatic peptide-surfactant interactions are required for coclustering and structure induction in the peptide and that the strength of the interaction depends on the surfactant net charge. Both aggregation-prone peptide-rich coclusters and stable surfactant-rich coclusters can form. Only Aβ(1-40) monomers, but not oligomers, are inserted into surfactant micelles in this surfactant-rich state. Surfactant headgroup charge is suggested to be important as electrostatic peptide-surfactant interactions on the micellar surface seems to be an initiating step toward insertion. Thus, no peptide insertion or change in peptide secondary structure is observed using a nonionic surfactant. The hydrophobic peptide-surfactant interactions instead stabilize the Aβ monomer, possibly by preventing self-interaction between the peptide core and C-terminus, thereby effectively inhibiting the peptide aggregation process. These findings give increased understanding regarding the molecular driving forces for Aβ aggregation and the peptide interaction with amphiphilic biomolecules.
(Less)
- author
- Österlund, Nicklas
; Kulkarni, Yashraj S
; Misiaszek, Agata D
; Wallin, Cecilia
; Krüger, Dennis M
; Liao, Qinghua
; Mashayekhy Rad, Farshid
; Jarvet, Jüri
; Strodel, Birgit
; Wärmländer, Sebastian K T S
; Ilag, Leopold L
; Kamerlin, Shina C L
LU
and Gräslund, Astrid
(Less) - publishing date
- 2018-07-18
- type
- Contribution to journal
- publication status
- published
- keywords
- Amyloid beta-Peptides/chemistry, Animals, Humans, Hydrophobic and Hydrophilic Interactions, Micelles, Molecular Dynamics Simulation, Protein Aggregation, Pathological/drug therapy, Protein Structure, Secondary, Static Electricity, Surface-Active Agents/chemistry
- in
- ACS Chemical Neuroscience
- volume
- 9
- issue
- 7
- pages
- 13 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:29683649
- scopus:85046468820
- ISSN
- 1948-7193
- DOI
- 10.1021/acschemneuro.8b00065
- language
- English
- LU publication?
- no
- id
- b2931727-b1c7-47e0-a334-d88a6ee3392f
- date added to LUP
- 2025-01-11 21:16:28
- date last changed
- 2025-05-18 14:54:07
@article{b2931727-b1c7-47e0-a334-d88a6ee3392f,
abstract = {{<p>The amphiphilic nature of the amyloid-β (Aβ) peptide associated with Alzheimer's disease facilitates various interactions with biomolecules such as lipids and proteins, with effects on both structure and toxicity of the peptide. Here, we investigate these peptide-amphiphile interactions by experimental and computational studies of Aβ(1-40) in the presence of surfactants with varying physicochemical properties. Our findings indicate that electrostatic peptide-surfactant interactions are required for coclustering and structure induction in the peptide and that the strength of the interaction depends on the surfactant net charge. Both aggregation-prone peptide-rich coclusters and stable surfactant-rich coclusters can form. Only Aβ(1-40) monomers, but not oligomers, are inserted into surfactant micelles in this surfactant-rich state. Surfactant headgroup charge is suggested to be important as electrostatic peptide-surfactant interactions on the micellar surface seems to be an initiating step toward insertion. Thus, no peptide insertion or change in peptide secondary structure is observed using a nonionic surfactant. The hydrophobic peptide-surfactant interactions instead stabilize the Aβ monomer, possibly by preventing self-interaction between the peptide core and C-terminus, thereby effectively inhibiting the peptide aggregation process. These findings give increased understanding regarding the molecular driving forces for Aβ aggregation and the peptide interaction with amphiphilic biomolecules.</p>}},
author = {{Österlund, Nicklas and Kulkarni, Yashraj S and Misiaszek, Agata D and Wallin, Cecilia and Krüger, Dennis M and Liao, Qinghua and Mashayekhy Rad, Farshid and Jarvet, Jüri and Strodel, Birgit and Wärmländer, Sebastian K T S and Ilag, Leopold L and Kamerlin, Shina C L and Gräslund, Astrid}},
issn = {{1948-7193}},
keywords = {{Amyloid beta-Peptides/chemistry; Animals; Humans; Hydrophobic and Hydrophilic Interactions; Micelles; Molecular Dynamics Simulation; Protein Aggregation, Pathological/drug therapy; Protein Structure, Secondary; Static Electricity; Surface-Active Agents/chemistry}},
language = {{eng}},
month = {{07}},
number = {{7}},
pages = {{1680--1692}},
publisher = {{The American Chemical Society (ACS)}},
series = {{ACS Chemical Neuroscience}},
title = {{Amyloid-β Peptide Interactions with Amphiphilic Surfactants : Electrostatic and Hydrophobic Effects}},
url = {{http://dx.doi.org/10.1021/acschemneuro.8b00065}},
doi = {{10.1021/acschemneuro.8b00065}},
volume = {{9}},
year = {{2018}},
}