Modification of Liposomal Properties by an Engineered Gemini Surfactant

Lipid membranes form the primary structure of cell membranes and serve as configurable interfaces across numerous applications including biosensing technologies, antifungal treatments, and therapeutic platforms. Therefore, the modification of lipid membranes by additives has important consequences in both biological processes and practical applications. In this study, we investigated a nicotinic-acid–based gemini surfactant (NAGS) as a chemically tunable molecular additive for modulating the structure and phase behavior of liposomal membranes. We specifically focused on NAGS with hydrocarbon chains that mirror those of lipid molecules. By introducing NAGS to phosphatidylcholine membranes with lipids of identical and varied chain lengths or degrees of unsaturation, we demonstrated the effects of headgroup interactions and chain mismatch between NAGS and membrane lipids. Using small-angle X-ray scattering, we showed that regardless of chain compatibility or mismatch, NAGS reduced the thickness and packing density of fluid lipid membranes. Further observations by fluorescence microscopy revealed the emergence of ordered-disordered domains upon cooling to room temperature. The observed phases were quite distinct from those of lipid membranes with analogous chain compositions, emphasizing the importance of NAGS headgroup chemistry in mediating domain formation and stabilization. These findings open new possibilities for exploiting NAGS in tuning the structure and organization of liposomal membranes with potential applications in drug delivery and biomedical imaging.