Measuring the Interactions and Influence of Amphipathic Copolymers with Lipid Monolayers and Bilayers as Models of Biological Membranes

Amphipathic copolymers are useful materials for nanomedicine, owing to their ability to self-assemble into nanoparticles, act as surfactants for inorganic materials, or for their favorable interactions with lipid membranes. Despite their widespread use, there is still a range of questions about the physicochemical properties that are necessary to drive their interactions at biological interfaces. To fully understand these interactions requires a diverse range of complementary analytical techniques. In this work, a library of neutral amphipathic methacrylate copolymers is synthesized by reversible addition-fragmentation chain-transfer polymerization (RAFT) polymerization, to investigate the effect of polymer composition and nature of the hydrophobic comonomer on interactions with model lipid membranes. These materials are shown to interact with Langmuir lipid monolayers, and neutron reflectometry demonstrates that hydrophobic interactions lead to the polymers intercalating with the monolayers. More complex models of lipid bilayers are studied using an in situ quartz crystal microbalance (QCM) model and shows while the composition and hydrophobic comonomer affect the stability of these interactions, there is no effect on the viscoelasticity of the lipid membranes. The in-depth understanding of these interfacial interactions afforded by this suite of analytical tools will allow for more complex copolymers to be studied, providing a greater understanding of key processes in nanomedicine, such as cellular entry and endosomal escape. A library of amphipathic methacrylic copolymers is synthesized and tested for their effects on models of cell membranes. The polymer-membrane interactions are studied using complementary techniques in Langmuir monolayers, neutron reflectometry, and QCM-D. A complete understanding of the impact of amphipathic copolymers on cell membranes is critical to improve amphipathic polymers for use as nanomedicines.image