Interaction Between Ionic Liquids and Lipid Membranes: A Comparative Analysis of the Mechano-Elastic Properties of Membranes as a Function of the Molecular Structure of Ionic Liquids Using Atomic Force Microscopy

Abstract

This dissertation investigates the intricate interactions between ionic liquids (ILs) and cell membranes, employing dimyristoylphosphatidylcholine (DMPC) lipid bilayers as a model biomembrane. The research focuses on the mechano-elastic properties of lipid bilayers and examines how these properties are influenced by the molecular structures of three ILs: 1 butyl-3-methylimidazolium chloride tetrachloroferrate ([bmim][FeCl4]), ([bmim][Cl]), 1-butyl-3-methylimidazolium and 1-decyl-3-methylimidazolium chloride ([dmim][Cl]). Advanced atomic force microscopy (AFM) methodologies, including force spectroscopy and off-resonance imaging, were utilised to generate high-resolution data on bilayer morphology and mechanical properties. By leveraging AFM, the study elucidates the effects of variations in cation alkyl chain length and anion size on membrane stability, fluidity, elasticity and rupture force. The ILs investigated demonstrate distinctive impacts on the DMPC lipid bilayer. [bmim][Cl] and [bmim][FeCl4], which share the same cation, induce comparable destabilising effects, such as decreasing in rupture force and increasing in softening, attributable to their interactions with lipid headgroups. In contrast, [dmim][Cl], distinguished by its longer alkyl chain, enhances bilayer stiffness and rupture force, underscoring the critical role of hydrophobic interactions and alkyl chain penetration into the bilayer core. The findings highlight the dual influence of cations and anions on the mechano-elastic properties of lipid bilayers, providing insights into their mechanisms of action. This thesis also explores the cytotoxicity of ILs using MTT assays on breast cancer MDA MB-231 cells, identifying subtoxic concentrations suitable for biomembrane models doping studies. The results contribute to a broader understanding of IL-biomembrane interactions, offering implications for their application in biomedical and pharmaceutical fields, such as drug delivery systems. The research paves the way for the development of IL-based therapeutic strategies targeting cancer cell membranes and provides a foundation for further exploration of ILs in biophysical and biomedical contexts