Interaction of amphiphilic block copolymers with abiotic lipid membranes and with cells

Certain commercial block copolymers in the poloxamer class (e.g., triblocks of poly(ethylene oxide) PEO and poly(propylene oxide) PPO) are known to interact with cell membranes, with either stabilizing or disruptive effects, depending on the situation. However, the mechanisms by which these effects arise are not yet established. In a broad effort to elucidate the key molecular variables, we have quantified the extent binding of a variety of PEO-PPO diblocks and triblocks with model lipid membranes, using pulsed-field-gradient NMR. In addition to these architectural variants, we have examined less hydrophilic blocks such as poly(butylene oxide) PBO, and also novel bottlebrush poloxamers. The ability of certain poloxamers to modulate lipid bilayer mechanical properties has been quantified using a micropipette aspiration assay. In order to relate the degree of binding to therapeutic efficacy, these molecules have also been compared in their ability to stabilize cell membranes against oxidative stress. The lessons learned from these various studies will be discussed, and remaining questions highlighted