Effects of ionic liquids on the nanoscopic dynamics and phase behaviour of a phosphatidylcholine membrane

Abstract

Ionic liquids (ILs) are potential candidates for new antimicrobials due to their tunable antibacterial and antifungal properties that are required to keep pace with the growing challenge of bacterial resistance. To a great extent their antimicrobial actions are related to the interactions of ILs with cell membranes. Here, we report the effects of ILs on the nanoscopic dynamics and phase behaviour of a dimyristoylphosphatidylcholine (DMPC) membrane, a model cell membrane, as studied using neutron scattering techniques. Two prototypical imidazolium-based ILs 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM[BF4]) and 1-decyl-3-methylimidazolium tetrafluoroborate (DMIM[BF4]), which differ only in terms of the alkyl chain length of cations, have been used for the present study. Fixed Elastic Window Scan (FEWS) shows that the incorporation of ILs affects the phase behaviour of the phospholipid membrane significantly and the transition from a solid gel to a fluid phase shifts to lower temperature. This is found to be consistent with our differential scanning calorimetry measurements. DMIM[BF4], which has a longer alkyl chain cation, affects the phase behaviour more strongly in comparison to BMIM[BF4]. The pressure-area isotherms of the DMPC monolayer measured at the air-water interface show that in the presence of ILs, isotherms shift towards higher area-per lipid molecule. DMIM[BF4] is found to shift the isotherm to a greater extent compared to BMIM[BF4]. Quasielastic neutron scattering (QENS) data show that both ILs act as a plasticizer, which enhances the fluidity of the membrane. DMIM[BF4] is found to be a stronger plasticizing agent in comparison to BMIM[BF4] that has a cation with a shorter alkyl chain. The incorporation of DMIM[BF4] enhances not only the long range lateral motion but also the localised internal motion of the lipids. On the other hand, BMIM[BF4] acts weakly in comparison to DMIM[BF4] and mainly alters the localised internal motion of the lipids. Any subtle change in the dynamical properties of the membrane can profoundly affect the stability of the cell. Hence, the dominant effect of the IL with the longer chain length on the dynamics of the phospholipid membrane might be correlated with its cytotoxic activity. QENS data analysis has provided a quantitative description of the effects of the two imidazolium-based ILs on the dynamical and phase behaviour of the model cell membrane, which is essential for a detailed understanding of their action mechanism.

Dioctadecyldimethylammonium bromide, a surfactant model for the cell membrane: Importance of microscopic dynamics

“…Moreover, the solvent contribution is estimated by measuring QENS spectra from D 2 O alone. Thus, the scattering signal from the lipid membrane is obtained by subtracting that of the solvent as follows: 85,86 S mem ( Q , E ), S solution ( Q , E ), and S solvent ( Q , E ) are the scattering functions for the lipid membrane, total solution, and solvent, respectively. The factor, ϕ, takes into account the volume fraction of the solvent (D 2 O) in the solution.…”

Mechanisms of action of ionic liquids on living cells: the state of the art

“…A palette of very diverse experimental techniques as well as computational methods have been employed, including neutron and X-ray scattering, atomic force microscopy (AFM), fluorescence techniques, and molecular dynamics simulations (Evans 2008 ; Benedetto et al 2014a ; Benedetto et al 2014b ; Yoo et al 2014 ; Benedetto et al 2015 ; Yoo et al 2016a ; Yoo et al 2016b ; Wang et al 2016 ; Kontro et al 2016 ; Drücker et al 2017 ; Bhattacharya et al 2017 ; Witos et al 2017 ; Bornemann et al 2020 ). In this respect, quasi-elastic neutron scattering has been employed to determine the effect on lipid diffusion due to the presence of IL-cations into the lipid region, showing, for example, a reduction of liver lipid lateral motion in the presence of [C 10 mim][BF 4 ] (Sharma et al 2017 ; Sharma and Mukhopadhyay 2018 ; Bakshi et al 2020 ). In this context, neutron scattering, in tandem with computer simulations, can be a powerful and unique tool to investigate the chemical-physics of these systems (Magazù et al 2008 ; Magazù et al 2010 ; Magazù et al 2012 ; Nandi et al 2017 ; Benedetto and Ballone 2018b ).…”

Morphological and Interaction Characteristics of Surface‐Active Ionic Liquids and Palmitic Acid in Mixed Monolayers

“…While the interaction between [C n -mim]X and phospholipids has been explored extensively, [5,[26][27][28][29][30][31] basic research is still required in this area, particularly in understanding miscibility and the spatial distribution of binary mixed systems. To our knowledge, there have been no monolayer studies in the literature that investigate miscibility of SAILs with simple fatty acids, and the impact of mixing on film morphology.…”