Lipid Membrane Binding and Cell Protection Efficacy of Poly(1,2-butylene oxide)-b-poly(ethylene oxide) Copolymers

Nicholas J Van Zee, Amanda S. Peroutka, Adelyn Crabtree, Marc A Hillmyer, Timothy P. Lodge

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1433-1442
Number of pages10
JournalBiomacromolecules
Volume23
Issue number3
DOIs
StatePublished - Mar 14 2022

Bibliographical note

Funding Information:
This study was funded by the National Institute of Health (Grant R01 HL122323). NMR instrumentation was supported by the office of the Vice President of Research, College of Science and Engineering, and the Department of Chemistry at the University of Minnesota. The cryo-TEM images were taken as part of the Characterization Facility, College of Science and Engineering, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs. The authors acknowledge Julia Early and Letitia J. Yao for helpful discussions concerning PFG-NMR.

Publisher Copyright:
©

How much support was provided by MRSEC?

  • Shared

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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