Exploring the Heterogeneous Dynamical Environment at the Interface of Aβ₄₂ Peptide in Aqueous Ionic Liquid Solution

Area of Science:

• Biophysics
• Chemical Physics
• Materials Science

Background:

• Amyloid-β (Aβ) peptides are implicated in neurodegenerative diseases.
• Understanding Aβ aggregation is crucial for therapeutic development.
• Ionic liquids (ILs) are explored as potential agents to modulate peptide behavior.

Purpose of the Study:

• To investigate the heterogeneous dynamical environment of amyloid-β (Aβ42) peptide monomers in an aqueous solution containing the ionic liquid [BMIM][BF4].
• To elucidate the effect of the ionic liquid on the distribution and dynamics of water molecules and IL components around different peptide segments.
• To understand the role of electrostatic interactions in peptide-IL-water interactions.

Main Methods:

• Atomistic molecular dynamics (MD) simulations were performed on full-length Aβ42 peptide monomers.
• Simulations were conducted in a binary aqueous solution with 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) as a co-solvent.
• Analysis focused on water molecule and IL ion distribution, diffusion, reorientation, and hydrogen bond dynamics.

Main Results:

• The presence of [BMIM][BF4] induced locally heterogeneous and restricted water motions at the peptide interface.
• Water diffusion was faster around hydrophilic peptide segments (N-term, turn) than hydrophobic segments (hp1, hp2, C-term).
• IL components exhibited sluggish dynamics, with longer timescales for dynamic heterogeneity, particularly around polar peptide segments.

Conclusions:

• Ionic liquid [BMIM][BF4] significantly alters the hydration dynamics of Aβ42 peptides.
• Electrostatic interactions are key in mediating peptide-IL-water interactions, potentially inhibiting hydrophobic collapse and fibril formation.
• The findings offer insights into using ionic liquids for controlling amyloid peptide aggregation.