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Amyloid‑β Peptide Interactions with Amphiphilic Surfactants: Electrostatic and Hydrophobic Effects

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journal contribution
posted on 23.04.2018, 00:00 by Nicklas Österlund, Yashraj S. Kulkarni, Agata D. Misiaszek, Cecilia Wallin, Dennis M. Krüger, Qinghua Liao, Farshid Mashayekhy Rad, Jüri Jarvet, Birgit Strodel, Sebastian K. T. S. Wärmländer, Leopold L. Ilag, Shina C. L. Kamerlin, Astrid Gräslund
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.

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