Inhibition of Aβ16–22 Aggregation by [TEA]+[Ms]− Follows Weakening of the Hydrophobic Core and Sequestration of Peptides in Ionic Liquid Nanodomains

• Published in: The journal of physical chemistry. B 2024-09, Vol.128 (38), p.9143-9150
• Main Authors: Lee, Pei-Yin, Gotla, Suhas, Matysiak, Silvina
• Format: Article
• Language: English
• Subjects: amyloid; B: Biophysical and Biochemical Systems and Processes; hydrophobicity; ionic liquids; liquids; molecular dynamics; nanomaterials; peptides; phenylalanine
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/acs.jpcb.4c05135

We developed a coarse-grained model for the protic ionic liquid, triethylammonium mesylate ([TEA]+[Ms]−), to characterize its inhibitory effects on amyloid aggregation using the K16LVFFAE22 fragment of the amyloid-β (Aβ16–22) as a model amyloidogenic peptide. In agreement with previous experiments, coarse-grained molecular dynamics simulations showed that increasing concentrations of [TEA]+[Ms]− in aqueous media led to increasingly small Aβ16–22 aggregates with low beta-sheet contents. The cause of [TEA]+[Ms]−’s inhibition of peptide aggregation was found to be a result of two interrelated effects. At a local scale, the enrichment of interactions between [TEA]+ cations and hydrophobic phenylalanine side chains weakened the hydrophobic cores of amyloid aggregates, resulting in poorly ordered structures. At a global level, peptides tended to localize at the interfaces of IL-rich nanostructures with water. At high IL concentrations, when the IL–water interface was large or fragmented, Aβ16–22 peptides were dispersed in the simulation cell, sometimes sequestered at unaggregated monomeric states. Together, these phenomena underlie [TEA]+[Ms]−’s inhibition of amyloid aggregation. This work addresses the critical lack of knowledge on the mechanisms of protein–ionic liquid interactions and may have broader implications for industrial applications.