Multiple poloxamers increase plasma membrane repair capacity in muscle and nonmuscle cells

Thomas A. Kwiatkowski, Aubrey L. Rose, Rachel Jung, Ana Capati, Diana Hallak, Rosalie Yan, Noah Weisleder

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Various previous studies established that the amphiphilic tri-block copolymer known as poloxamer 188 (P188) or Pluronic-F68 can stabilize the plasma membrane following a variety of injuries to multiple mammalian cell types. This characteristic led to proposals for the use of P188 as a therapeutic treatment for various disease states, including muscular dystrophy. Previous studies suggest that P188 increases plasma membrane integrity by resealing plasma membrane disruptions through its affinity for the hydrophobic lipid chains on the lipid bilayer. P188 is one of a large family of copolymers that share the same basic tri-block structure consisting of a middle hydrophobic propylene oxide segment flanked by two hydrophilic ethylene oxide moieties [poly(ethylene oxide)80-poly(propylene oxide)27-poly(ethylene oxide)80]. Despite the similarities of P188 to the other poloxamers in this chemical family, there has been little investigation into the membrane-resealing properties of these other poloxamers. In this study we assessed the resealing properties of poloxamers P181, P124, P182, P234, P108, P407, and P338 on human embryonic kidney 293 (HEK293) cells and isolated muscle from the mdx mouse model of Duchenne muscular dystrophy. Cell membrane injuries from glass bead wounding and multiphoton laser injury show that the majority of poloxamers in our panel improved the plasma membrane resealing of both HEK293 cells and dystrophic muscle fibers. These findings indicate that many tri-block copolymers share characteristics that can increase plasma membrane resealing and that identification of these shared characteristics could help guide design of future therapeutic approaches.

Original languageEnglish
Pages (from-to)C253-C262
JournalAmerican Journal of Physiology - Cell Physiology
Volume318
Issue number2
DOIs
StatePublished - 2020

Bibliographical note

Publisher Copyright:
© 2020 the American Physiological Society.

Funding

This work was supported by a Research Grant from the Muscular Dystrophy Association (N. Weisleder) and by National Institute on Aging of the National Institutes of Health under Award Number R01AG056504 (N. Weisleder). The Campus Microscopy and Imaging Facility of The Ohio State University is supported in part by NIH National Cancer Institute Grant P30 CA016058. This project was also supported by The Ohio State University Ross Heart Hospital TriFit Challenge.

FundersFunder number
National Institutes of Health (NIH)
National Institute on AgingR01AG056504
National Childhood Cancer Registry – National Cancer InstituteP30 CA016058
Muscular Dystrophy Association

    Keywords

    • Membrane repair
    • Muscular dystrophy; P188; poloxamers
    • Rotation damage assay

    ASJC Scopus subject areas

    • Physiology
    • Cell Biology

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