Ionic liquids meet lipid bilayers: a state-of-the-art review.

In the past 25 years, a vast family of complex organic salts known as room-temperature ionic liquids (ILs) has received increasing attention due to their potential applications. ILs are composed by an organic cation and either an organic or inorganic anion, and possess several intriguing properties such as low vapor pressure and being liquid around room temperature. Several biological studies flagged their moderate-to-high (cyto)-toxicity. Toxicity is, however, also a synonym of affinity, and this boosted a series of biophysical and chemical-physical investigations aimed at exploiting ILs in bio-nanomedicine, drug-delivery, pharmacology, and bio-nanotechnology. Several of these investigations focused on the interaction between ILs and lipid membranes, aimed at determining the microscopic mechanisms behind their interaction. This is the focus of this review work. These studies have been carried out on a variety of different lipid bilayer systems ranging from 1-lipid to 5-lipids systems, and also on cell-extracted membranes. They have been carried out at different chemical-physical conditions and by the use of a number of different approaches, including atomic force microscopy, neutron and X-ray scattering, dynamic light scattering, differential scanning calorimetry, surface quartz microbalance, nuclear magnetic resonance, confocal fluorescence microscopy, and molecular dynamics simulations. The aim of this "2023 Michèle Auger Award" review work is to provide the reader with an up-to-date overview of this fascinating research field where "ILs meet lipid bilayers (aka biomembranes)," with the aim to boost it further and expand its cross-disciplinary edges towards novel high-impact ideas/applications in pharmacology, drug delivery, biomedicine, and bio-nanotechnology.