Poloxamers consisting of poly­(ethylene oxide) (PEO) and poly­(propylene oxide) segments can protect cell membranes against various forms of stress. We investigated the role of the hydrophobic block chemistry on polymer/membrane binding and cell membrane protection by comparing a series of poly­(butylene oxide)-b-PEO (PBO-b-PEO) copolymers to poloxamer analogues, using a combination of pulsed-field-gradient (PFG) NMR experiments and a lactate dehydrogenase (LDH) cell assay. We found that the more hydrophobic PBO-b-PEO copolymers bound more significantly to model liposomes composed of 1-palmitol-2-oleoyl-glycero-3-phosphocholine (POPC) compared to poly­(propylene oxide) (PPO)/PEO copolymers. However, both classes of polymers performed similarly when compared by an LDH assay. These results present an important comparison between polymers with similar structures but with different binding affinities. They also provide mechanistic insight as enhanced polymer/lipid membrane binding did not directly translate to increased cell protection in the LDH assay, and therefore, additional factors need to be considered when trying to achieve greater membrane protection efficacy.

Poloxamers, also known by their trade name, Pluronics, are known to mitigate damage to cellular membranes. However, the mechanism underlying this protection is still unclear. We investigated the effect of poloxamer molar mass, hydrophobicity, and concentration on the mechanical properties of giant unilamellar vesicles, composed of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine, using micropipette aspiration (MPA). Properties including the membrane bending modulus (κ), stretching modulus (K), and toughness are reported. We found that poloxamers tend to decrease K, with an impact largely dictated by their membrane affinity, i.e., both a high molar mass and less hydrophilic poloxamers depress K at lower concentrations. However, a statistically significant effect on κ was not observed. Several poloxamers studied here showed evidence of membrane toughening. Additional pulsed-field gradient NMR measurements provided insight into how polymer binding affinity connects to the trends observed by MPA. This model study provides important insights into how poloxamers interact with lipid membranes to further understanding of how they protect cells from various types of stress. Furthermore, this information may prove useful for the modification of lipid vesicles for other applications, including use in drug delivery or as nanoreactors.