Imidazolium-Based Ionic Liquids Affect Morphology and Rigidity of Living Cells: an Atomic Force Microscopy Study

The study of the toxicity, biocompatibility, and environmental sustainability of room-temperature Ionic Liquids (ILs) is still in its infancy. Understanding the impact of ILs on living organisms, especially from the aquatic ecosystem, is urgent, since on one side large amounts of these substances are widely employed as solvents in industrial chemical processes, and on the other side evidences of toxic effects of ILs on microorganisms and single cells have been observed. To date, the toxicity of ILs have been investigated by means of macroscopic assays aimed at characterizing the effective concentrations (like the EC50) that cause the dead of a significant fraction of the population of microorganisms and cells. These studies allowed to identify the cell membrane as the first target of the IL interaction, whose effectiveness was correlated to the lipophilicity of the cation, i.e. to the length of the lateral alkyl chain. Our study aimed at characterizing the molecular mechanisms of the toxicity of ILs. To this purpose, we carried out a combined topographic and mechanical analysis by Atomic Force Microscopy of living breast metastatic cancer cells (MDA-MB-231) upon interaction with imidazolium-based ILs. We showed that ILs are able to induce modifications of the overall rigidity (effective Young modulus) and morphology of the cells. Our results demonstrate that ILs act on the physical properties of the cell membrane, and possibly induce cytoskeletal reorganization, already at concentrations below the EC50. These potentially toxic effects are stronger at higher IL concentrations, as well as with longer lateral chains in the cation.<br>