A biophysical study of the effect of ionic liquids on bio-membranes and cells by means of atomic force microscopy, neutron scattering, computational and biological approaches

The effect of organic salts of low melting temperature, called ionic liquids (ILs), on mechanoelasticity of cell membranes and migration of cells have been investigated by a combination of experimental approaches, including neutron scattering and atomic force microscopy (AFM), complemented by biological assays; nanostructuring of ILs in water solution and optical properties of ILs relevant for biological applications have been investigated by computational approaches, including molecular dynamics (MD) simulations and density functional methods. A major part of this Ph.D. work focuses on the effect of sub-toxic concentration of imidazolium ILs of varying chain length ([bmim][Cl] and [dmim][Cl]). At the IL concentrations below their critical micellar concentration, a combined neutron scattering and AFM studies showed insertion of [bmim][Cl] IL-cation into the lipid bilayer and affecting their local mechano-elasticity in IL chain-length dependent manner. Additionally, in-vitro cell migration assay has resulted in the IL-induced enhancement of cell migration rate depending upon their chain-length and concentration. Overall, these effects are stronger for the longer chain-length and the highest sub-toxic concentration of the ILs. Combining these biophysical and biochemical studies, we propose, in the end, a bio-chemical-physical mechanism that relates this IL-induced alteration in the cell membrane with the alteration in the cell migration. The overall result is that IL-concentration and IL-cation chain-length can tune the cell membrane elasticity and cell migration. The chemical-physical manipulations of the lipid-bilayer elasticity hold the promise of effective therapeutic and diagnostic approaches. The chemical-physics background underlying the complex phenomena explored previously by experiments has been investigated by computational means, focusing on the nanostructuring in the water of protic and aprotic ILs. Here, by employing MD simulations based on empirical force fields, we analysed the fluctuations of the ions and water molecule distribution in space in solutions spanning a wide salt concentration range, from 25 to 75 wt%. Depending upon the salt concentration, the transition of nanostructuring from water-rich to salt-rich condition has been observed. Additionally, a combination of density functional methods has been used to compute absorption and luminescence properties of gas-phase single ions and neutral ion pairs from ILs.