Abstract
Ionic liquids (ILs) are considered to be green solvents because of their non-volatility. Although ILs are relatively safe in the atmospheric environment, they may be toxic in other environments. Our previous research showed that the cytotoxicity of ILs to biological organisms is attributable to interference with cell membranes by IL insertion. However, the effects of ILs on ion channels, which play important roles in cell homeostasis, have not been comprehensively studied to date. In this work, we studied the interactions between ILs and lipid bilayer membranes with gramicidin A ion channels. We used two methods, namely electrical and fluorescence measurements of ions that permeate the membrane. The lifetimes of channels were increased by all the ILs tested in this work via stabilizing the compressed structure of the lipid bilayer and the rate of ion flux through gA channels was decreased by changing the membrane surface charge. The former effect, which increased the rate of ion flux, was dominant at high salt concentrations, whereas the latter, which decreased the rate of ion flux, was dominant at low salt concentrations. The effects of ILs increased with increasing concentration and alkyl chain length. The experimental results were further studied using molecular dynamics simulations.
Highlights
Ionic liquids (ILs) are salts that are in the liquid state below 100 °C; they consist of organic cations and inorganic anions, and have wide liquid-temperature ranges
The rate of ion flux through gramicidin A (gA) channels and the lifetime of the gA dimer are affected by the surface charge and compressed structure of lipid bilayer near the gA dimer, respectively[19,20]
Neighboring phospholipids are compressed on dimerization, because the length of the gA dimer is less than the membrane thickness
Summary
Ionic liquids (ILs) are salts that are in the liquid state below 100 °C; they consist of organic cations and inorganic anions, and have wide liquid-temperature ranges. To obtain experimental results at low salt concentrations, we conducted fluorescence experiments using liposomes containing a fluorophore In both experiments, the longer the hydrocarbon carbon chain and the higher the concentration of ILs were, the more effectively the rate of ion flux through gA channels changed. The presence of ILs stabilizes the gA dimer and allows the permeation of more ions by increasing channel openning time, but ILs change the membrane surface charge, which decreases rate of cation flux through each gA ion channel. Both effects occur at the same time, one dominates over the other depending on ionic strength of solvents. Our research will help to determine the appropriate alkyl chain length and functional head groups of ILs to discover more biocompatible ionic liquids[21,22]
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