Explicit Solvent Effects on Ion Selectivity and Membrane Potential of Charged Spherical Liposomes: A Classical Density-Functional Theory Investigation

Abstract In this work, we use classical density-functional theory (CDFT) to study ion selectivity and membrane potential in cationic and anionic spherical liposomes. The influence of surface charge, electrolyte concentration, cavity size, and solvent structure on these properties has been systematically studied. The liposomes are modeled as charged spherical vesicles with phospholipid bilayer membranes having cationic/anionic surface charges. To demonstrate solvent-mediated electrostatic effects, two complementary solvent descriptions are considered: the restricted primitive model (RPM), where the solvent is treated as a dielectric continuum, and the solvent-restricted primitive model (SRPM), where solvent molecules are explicitly represented as neutral hard spheres. Ion selectivity (χi) and membrane potential (ψMP) are systematically evaluated for liposomes in equilibrium with binary AB and CB2 electrolyte mixtures over a broad range of surface charge densities, electrolyte concentrations, and cavity sizes. Ion selectivity is improved by the surface charge, while the increasing electrolyte concentration reduces ion selectivity due to stronger electrostatic screening and enhanced ion–ion correlations, which modify ionic distributions within the liposome cavity. The selectivity is generally decreased with the increase of cavity sizes. Also, the predicted selectivity parameter by SRPM is smaller than that of RPM. The nonlinear behaviors for membrane potentials with charge inversion are observed under the situation of highly concentrated electrolytes. In contrast to the continuum-based RPM, the explicit solvent SRPM captures reduced magnitudes of membrane potentials correctly and describes charge inversion better by including solvent-packing and excluded-volume effects. These results give new insights into the solvent-mediated electrostatic interactions in confined lipid systems and provide a theoretical basis to understand the ion selectivity properties in charged liposomes.