Mixing Block Copolymers with Phospholipids at the Nanoscale: From Hybrid Polymer/Lipid Wormlike Micelles to Vesicles Presenting Lipid Nanodomains

Hybrid, i.e. intimately mixed polymer/phospholipid vesicles can potentially marry in a single membrane the best characteristics of the two separate components. The ability of amphiphilic copolymers and phospholipids to self-assemble into hybrid membranes has been studied until now at the sub-micron scale using optical microscopy on Giant Hybrid Unilamellar Vesicles (GHUVs), but limited information is available on Large Hybrid Unilamellar Vesicles (LHUVs). In this work, copolymers based on poly(dimethyl siloxane) and poly(ethylene oxide) with different molar masses and architectures (graft, triblock) were associated with 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC). Classical protocols of LUV formation were used to obtain nano-sized self-assembled structures. Using Small Angle Neutron Scattering (SANS), Time Resolved Förster Resonance Energy Transfer (TR-FRET) and Cryo-Transmission Electron Microscopy (Cryo-TEM), we show that copolymer architecture and molar mass have a direct consequence on the formation of hybrid nanostructures that can range from worm-like hybrid micelles to hybrid vesicles presenting small lipid nanodomains