(176f) Phase Coexistence in Hybrid Lipid/Block Copolymer Biomembranes

Hybrid biomembranes composed of phospholipids and block copolymers have shown potential promise as drug delivery vehicles combining the inherent biocompatibility of lipids with the durability and chemical diversity of block copolymers. Mixing these materials to form hybrid biomembranes could aid the continued development of stimuli-responsive membranes (e.g. pH- or thermo-responsive systems) to increase the efficacy of liposomal drug delivery vehicles. However, there has been little work exploring the phase behavior of such hybrid biomembranes on biologically relevant, sub-micron length scales, despite the implications toward membrane surface architecture and thus membrane function. To this end, we have studied small (~100 nm) vesicles made of polybutadiene-block-polyethylene oxide (PBd-PEO) and dipalmitoylphosphatidylcholine (DPPC) using fluorescence spectroscopy techniques. The fluorescent probes diphenylhexatriene (DPH) and 6-dodecanoyl-2-dimethylaminonaphthalene (laurdan) provide information regarding membrane fluidity and polarity as functions of membrane composition and temperature. The efficiency of Förster resonance energy transfer (FRET) between fluorescent probes expected to prefer the lipid- or polymer-rich phase was also evaluated to more directly investigate the presence of demixing in nanoscale vesicles. Using these methods to map the phase behavior of hybrid biomembranes as a function of temperature and composition suggests small vesicles demonstrate coexisting lipid-rich and copolymer-rich domains. These methods will be further applied to evaluate pH-driven mixing and demixing of hybrid biomembranes, with the ultimate goal of obtaining a more fundamental understanding of their phase behavior and facilitating a more informed approach to the design of stimuli-responsive membranes.