Unraveling the Phase Behavior, Mechanical Stability, and Protein Reconstitution Properties of Polymer-Lipid Hybrid Vesicles

Hybrid vesicles consistingof natural phospholipids and syntheticamphiphilic copolymers have shown remarkable material properties andpotential for biotechnology, combining the robustness of polymerswith the biocompatibility of phospholipid membranes. To predict andoptimize the mixing behavior of lipids and copolymers, as well asunderstand the interaction between the hybrid membrane and macromoleculeslike membrane proteins, a comprehensive understanding at the molecularlevel is essential. This can be achieved by a combination of moleculardynamics simulations and experiments. Here, simulations of POPC andPBD(22)-b-PEO14 hybrid membranesare shown, uncovering different copolymer configurations dependingon the polymer-to-lipid ratio. High polymer concentrations createdthicker membranes with an extended polymer conformation, while highlipid content led to the collapse of the polymer chain. High concentrationsof polymer were further correlated with a decreased area compressionmodulus and altered lateral pressure profiles, hypothesized to resultin the experimentally observed improvement in membrane protein reconstitutionand resistance toward destabilization by detergents. Finally, simulationsof a WALP peptide embedded in the bilayer showed that only membraneswith up to 50% polymer content favored a transmembrane configuration.These simulations correlate with previous and new experimental resultsand provide a deeper understanding of the properties of lipid-copolymerhybrid membranes.

Automated summary

Hybrid vesicles combining natural phospholipids and synthetic amphiphilic copolymers have great potential in biotechnology due to their unique material properties. Molecular dynamics simulations and experiments have been used to investigate the interactions between lipids and copolymers, as well as the effects on membrane protein reconstitution and resistance to destabilization by detergents.