Modulating the Phase Properties of Biomimetic Ion Pair Amphiphile Membranes

Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic surfactants, can self-assemble into catanionic vesicles as potential liposome surrogates. Like lipid bilayers, an IPA membrane can be in either fluidic liquid-disorder (L_α) phase or in solid-like gel (L_β) phase when above or below the main phase transition temperature (T_m), respectively. Modulating the phase behaviours of the IPA vesicles is thus critical for its delivery applications. Here, we utilized molecular simulations to systematically examine the phase properties of IPA bilayers with various compositions. Via varying the alkyl chain asymmetry, we first characterized the T_m response of the membranes to IPA mixtures and found deviations from the ideal mixture. Such deviation is partly originated from the transition between the tilted and non-tilted gel phases induced by IPA mixing. We further modulated the compositions of ionic charged groups of IPAs. Using molecular simulations, we constructed the database for the solvation free energies of various ions and the association free energies of possible ion pairs. Applying the law of matching water affinities (LMWA), we screened ion pair candidates to from pH responsive IPA membranes. Our simulations suggested that IPA membranes are most stable at pH = pKa of one of the components. The combined results provide useful insights into the designs of catanionic vesicles with the stimuli-responsive potentials, benefiting the future development of novel drug carriers.