Influence of the Headgroup on the Interaction of Poly(ethylene oxide)-Poly(propylene oxide) Block Copolymers with Lipid Bilayers

The lipid headgroup plays an important role in the association of polymers with lipid bilayer membranes. Herein, we report how a glycerol headgroup versus a choline headgroup affects the interaction of poly(ethylene oxide)-b-poly(propylene oxide) (PEO-PPO) block copolymers with lipid bilayer vesicles. Unilamellar vesicles composed of phosphatidylcholine and phosphatidylglycerol at various molar ratios were used as model membranes. The interactions between the block copolymers and lipid bilayers were quantified by pulsed-field gradient nuclear magnetic resonance (PFG-NMR) based on the distinctly different mobilities of free and bound polymers. All the investigated polymer species showed significantly higher binding with 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) sodium salt (POPG) liposomes than with 1palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes, indicating stronger association with the glycerol headgroup compared to the choline headgroup. This effect did not become significant until the composition of mixed POPC/POPG liposomes contained more than 20 mol % POPG. A plausible explanation for the enhanced polymer binding with POPG invokes the role of hydrogen bonding between the glycerol headgroup and the ether moieties of the polymers.