The Effect of Lipid Phase Behavior on Polymer Binding to Liposomes

PEO-PPO block polymers interact with lipid bilayers and can have a stabilizing effect on cell membranes under stress. The stabilization mechanism is unknown but prior studies have found that numerous cell signaling pathways are upregulated and downregulated. Liposomes are useful membrane models because they can be prepared with custom compositions to probe the effect of different membrane components on polymer-lipid interactions. Prior research has shown that ternary mixtures with saturated/unsaturated lipids and cholesterol lead to phase coexistence. In this work, we leverage published ternary phase diagrams to explore the impact of lipid phase behavior on the binding of F127 to different membrane compositions of POPC, PSM, and cholesterol. Unimodal liposomes were prepared with vesicle extrusion diameter of 50 nm. Dynamic light scattering was used to validate the prepared liposomes, and PFG-NMR was used to quantify the amount of F127 bound to liposomes. We observed that cholesterol significantly reduced polymer binding to the liposomes relative to the POPC control. Addition of PSM also decreased binding non-monotonically. Compositions with Ld/Lo/So coexistence showed maximal binding of polymer, possibly because phase boundaries on the lipid bilayer are attractive binding sites.