Probing the Phase Behavior of Hybrid Lipid/Block Copolymer Biomembranes

Abstract

Hybrid biomembranes combining block copolymers and phospholipids have shown potential promise in the areas of drug delivery and membrane protein reconstitution. The chemical diversity afforded by inclusion of block copolymers is particularly relevant to the formation of stealth liposomes or stimuli-responsive membranes (e.g. pH- or thermo-responsive systems), which can aid in the control of drug retention and release. However, the phase behavior of these hybrid biomembranes has not been methodically explored. To this end, we have studied small (∼100 nm) vesicles and polymer-stabilized nanodiscs with membranes made of polybutadiene-block-polyethylene oxide (PBd-PEO) and dipalmitoylphosphatidylcholine (DPPC) using the fluorescent probes diphenylhexatriene (DPH) and 6-dodecanoyl-2-dimethylaminonaphthalene (laurdan). DPH and laurdan provide information regarding membrane fluidity, from which the ideality of mixing within the membrane can be determined. This method can be used to map the phase behavior of hybrid biomembranes over a range of temperatures and compositions, providing a more fundamental understanding of the phase states underlying observed behaviors of hybrid biomembranes and thus facilitating a more informed approach to their design.