Quantifying Ionic Liquid Affinity and Its Effect on Phospholipid Membrane Structure and Dynamics

TL;DR

This study investigates how imidazolium-based ionic liquids affect membrane structure and dynamics, revealing that longer alkyl chains increase membrane disorder, fluidity, and permeability, which correlates with higher toxicity.

Contribution

It provides a comprehensive experimental and simulation analysis of IL-induced membrane disorder, highlighting the role of alkyl chain length in modulating membrane properties.

Findings

ILs induce significant membrane disorder and lower phase transition temperatures.

Longer alkyl chains cause more pronounced membrane disruption and increased lipid diffusion.

Molecular dynamics simulations confirm experimental observations of membrane destabilization.

Abstract

In this study, we examine the impact of imidazolium based ILs on the viscoelasticity, dynamics, and phase behavior of two model membrane systems, (i) lipid monolayers and (ii) unilamellar vesicles composed of dipalmitoylphosphatidylcholine (DPPC). Our findings demonstrate that both ILs induce significant disorder in lipid membranes by altering the area per lipid molecule, thereby modulating their viscoelastic properties. ILs with longer alkyl chains show stronger interactions with membranes, causing more pronounced disorder. Fourier transform infrared spectroscopy indicates that IL incorporation shifts the membrane main phase transition to lower temperatures and introduces gauche defects, signifying increased structural disorder. This effect is amplified with longer alkyl chains and higher IL concentrations. Quasielastic neutron scattering studies highlight that ILs markedly enhance the lateral diffusion of lipids within the membrane leaflet, with the extent of enhancement determined by the membrane physical state, IL concentration, and alkyl chain length. The most pronounced acceleration in lateral diffusion occurs in ordered membrane phase with higher concentrations of the longer chain IL. Molecular dynamics simulations corroborate these experimental findings, showing that longer chain ILs extensively disrupt lipid organization, introduce more gauche defects, increase the area per lipid, and consequently enhance lateral diffusion. This increase in lipid fluidity and permeability provides a mechanistic basis for the observed higher toxicity associated with longer chain ILs.