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Amphiphilic Block Copolymer-Catalyzed Cell Membrane Sealing Is Linked to Decreased Membrane Tension


The cell plasma membrane suffers structural disruptions from both daily environmental stresses and trauma. Rapid loss of cell viability occurs if membrane integrity is not rapidly restored. Physiological membrane sealing involves alteration of local intermolecular thermodynamics that is manifested by changes in membrane tension which precede reassembly of the membrane planar bilayer structure. Certain block copolymer surfactants, including poloxamer 188 (P188), have been proven to seal-disrupted cell membranes. However, the specific molecular mechanics of poloxamer-mediated membrane sealing remains a target of investigation. A decrease in membrane tension precedes membrane sealing by natural intrinsic cell sealing processes. The effect of P188 on the quasistatic membrane tension of Madin-Darby canine kidney (MDCK) and Swiss 3T3 fibroblasts cells under normal and saponin-permeabilized conditions was measured using laser optical tweezer (LOT)-extracted membrane tethers. The tether trap length of saponin-permeabilized MDCK cell membranes decreased from an uninjured control of 11.28 ± 1.1 μm to 6.43 ± 0.67 μm. Treatment with P188 (0.2 mM) significantly increased the tether trap length to 9.69 ± 1.0 μm (p < 0.05) while the control polymer, polyethylene glycol (0.2 mM) resulted in tether trap length of 7.02 ± 0.73 μm that was not significantly different. Similar observations were made in the saponin-permeabilized fibroblasts. Corresponding fluorescence cell viability assays revealed that P188-treated cells had a higher survival rate. Thus, surfactant copolymer membrane sealing restores the membrane integrity by decreasing the membrane tension.

Lay Summary

Cells quickly become non-viable when plasma membrane integrity is lost. Restoring or healing the cell membrane requires alteration in the forces that stabilize the membrane structure. The membrane defect healing processes are preceded by a decrease in membrane interfacial tension. This study demonstrated that amphiphilic block copolymer surfactants, such as poloxamer 188 (P188), reduce membrane tension and promote cell survival. Using laser optical tweezers, this work quantified the effect of surfactant copolymer-catalyzed sealing. Our work utilized laser optical tweezers to demonstrate that copolymer-catalyzed membrane sealing corresponds with a decrease in membrane tension, much like the physiologic response to membrane injury.

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  1. Baskaran H, Toner M, Yarmush ML, Berthiaume F. Poloxamer-188 improves capillary blood flow and tissue viability in a cutaneous burn wound. J Surg Res. 2001;101:56–61.

    CAS  Article  Google Scholar 

  2. Chen HF, McFaul C, Tutushkin I, Cho M, Lee RC. Surfactant copolymer annealing of chemically permeabilized cell membranes. Regen Eng Transl Med. 2018.

  3. Cheng C-Y, Wang J-Y, Kausik R, Lee KYC, Han S. An ultrasensitive tool exploiting hydration dynamics to decipher weak lipid membrane–polymer interactions. J Magn Reson. 2012;215:115–9.

    CAS  Article  Google Scholar 

  4. Cheng C-Y, Wang J-Y, Kausik R, Lee KYC, Han S. Nature of interactions between PEO-PPO-PEO triblock copolymers and lipid membranes: (II) role of hydration dynamics revealed by dynamic nuclear polarization. Biomacromolecules. 2012;13:2624–33.

    CAS  Article  Google Scholar 

  5. Collins J, Despa F, Lee R. Structural and functional recovery of electropermeabilized skeletal muscle in-vivo after treatment with surfactant poloxamer 188. Biochim Biophys Acta Biomembr. 2007;1768:1238–46.

    CAS  Article  Google Scholar 

  6. Dai J, Sheetz MP. Cell membrane mechanics. Methods Cell Biol. 1997;55:157–71.

    Article  Google Scholar 

  7. Dai J, Sheetz MP, Wan X, Morris CE. Membrane tension in swelling and shrinking molluscan neurons. J Neurosci. 1998;18:6681–92.

    CAS  Article  Google Scholar 

  8. Diz-Muñoz A, Fletcher DA, Weiner OD. Use the force: membrane tension as an organizer of cell shape and motility. Trends Cell Biol. 2013;23:47–53.

    Article  Google Scholar 

  9. Fällman E, Schedin S, Jass J, Andersson M, Uhlin BE, Axner O. Optical tweezers based force measurement system for quantitating binding interactions: system design and application for the study of bacterial adhesion. Biosens Bioelectron. 2004;19:1429–37.

    Article  Google Scholar 

  10. Firestone MA, Seifert S. Interaction of nonionic PEO−PPO diblock copolymers with lipid bilayers. Biomacromolecules. 2005;6:2678–87.

    CAS  Article  Google Scholar 

  11. Frey SL, Zhang D, Carignano MA, Szleifer I, Lee KYC. Effects of block copolymer’s architecture on its association with lipid membranes: experiments and simulations. J Chem Phys. 2007;127:114904.

    Article  Google Scholar 

  12. Greenebaum B, Blossfield K, Hannig J, Carrillo CS, Beckett MA, Weichselbaum RR, et al. Poloxamer 188 prevents acute necrosis of adult skeletal muscle cells following high-dose irradiation. Burns. 2004;30:539–47.

    Article  Google Scholar 

  13. Hannig J, Zhang D, Canaday DJ, Beckett MA, Astumian RD, Weichselbaum RR, et al. Surfactant sealing of membranes permeabilized by ionizing radiation. Radiat Res. 2000;154:171–7.

    CAS  Article  Google Scholar 

  14. Hochmuth FM, Shao J-Y, Dai J, Sheetz MP. Deformation and flow of membrane into tethers extracted from neuronal growth cones. Biophys J. 1996;70:358–69.

    CAS  Article  Google Scholar 

  15. Lee RC, River LP, Pan F, Ji L, Wollmann RL. Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. Proc Natl Acad Sci. 1992;89:4524–8.

    CAS  Article  Google Scholar 

  16. Li Z, Anvari B, Takashima M, Brecht P, Torres JH, Brownell WE. Membrane tether formation from outer hair cells with optical tweezers. Biophys J. 2002;82:1386–95.

    CAS  Article  Google Scholar 

  17. Marks JD, Pan C-Y, Bushell T, Cromie W, Lee RC. Amphiphilic, tri-block copolymers provide potent membrane-targeted neuroprotection. FASEB J. 2001;15:1107–9.

    CAS  Google Scholar 

  18. Maskarinec SA, Hannig J, Lee RC, Lee KYC. Direct observation of poloxamer 188 insertion into lipid monolayers. Biophys J. 2002;82:1453–9.

    CAS  Article  Google Scholar 

  19. Matthews KL II, Aarsvold JN, Mintzer RA, Chen C-T, Lee RC. Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model. Burns. 2006;32:755–64.

    Article  Google Scholar 

  20. Merchant FA, Holmes WH, Capelli-Schellpfeffer M, Lee RC, Toner M. Poloxamer 188 enhances functional recovery of lethally heat-shocked fibroblasts. J Surg Res. 1998;74:131–40.

    CAS  Article  Google Scholar 

  21. Miyake K, McNeil PL. Mechanical injury and repair of cells. Crit Care Med. 2003;31:S496–501.

    Article  Google Scholar 

  22. Padanilam JT, Bischof JC, Lee RC, Cravalho EG, Tompkins RG, Yarmush ML, et al. Effectiveness of poloxamer 188 in arresting calcein leakage from thermally damaged isolated skeletal muscle cellsa. Ann N Y Acad Sci. 1994;720:111–23.

    CAS  Article  Google Scholar 

  23. Raucher D, Sheetz MP. Characteristics of a membrane reservoir buffering membrane tension. Biophys J. 1999;77:1992–2002.

    CAS  Article  Google Scholar 

  24. Shelat PB, Plant LD, Wang JC, Lee E, Marks JD. The membrane-active tri-block copolymer pluronic F-68 profoundly rescues rat hippocampal neurons from oxygen–glucose deprivation-induced death through early inhibition of apoptosis. J Neurosci. 2013;33:12287–99.

    CAS  Article  Google Scholar 

  25. Shilagardi K, Li S, Luo F, Marikar F, Duan R, Jin P, et al. Actin-propelled invasive membrane protrusions promote fusogenic protein engagement during cell-cell fusion. Science. 2013;340:359–63.

    CAS  Article  Google Scholar 

  26. Titushkin I, Cho M. Distinct membrane mechanical properties of human mesenchymal stem cells determined using laser optical tweezers. Biophys J. 2006;90:2582–91.

    CAS  Article  Google Scholar 

  27. Titushkin I, Cho M. Modulation of cellular mechanics during osteogenic differentiation of human mesenchymal stem cells. Biophys J. 2007;93:3693.

    CAS  Article  Google Scholar 

  28. Togo T. Long-term potentiation of wound-induced exocytosis and plasma membrane repair is dependant on cAMP-response element-mediated transcription via a protein kinase C- and p38 MAPK-dependent pathway. J Biol Chem. 2004;279:44996–5003.

    CAS  Article  Google Scholar 

  29. Togo T, Krasieva TB, Steinhardt RA. A decrease in membrane tension precedes successful cell-membrane repair. Mol Biol Cell. 2000;11:4339–46.

    CAS  Article  Google Scholar 

  30. Tsai MA, Frank RS, Waugh RE. Passive mechanical behavior of human neutrophils: effect of cytochalasin B. Biophys J. 1994;66:2166–72.

    CAS  Article  Google Scholar 

  31. Wang J-Y, Marks J, Lee KYC. Nature of interactions between PEO-PPO-PEO triblock copolymers and lipid membranes: effect of polymer hydrophobicity on its ability to protect liposomes from peroxidation. Biomacromolecules. 2012;13:2616–23.

    CAS  Article  Google Scholar 

  32. Wu G, Majewski J, Ege C, Kjaer K, Weygand M, Lee KYC. Interaction between lipid monolayers and poloxamer 188: an X-ray reflectivity and diffraction Study. Biophys J. 2005;89:3159–73.

    CAS  Article  Google Scholar 

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We would like to thank Julianna Oliveira and Hongfeng Chen, PhD, for conducting some experiments.


This work was financially supported by a National Institutes of Health grant GM RO1 64757 (RCL), National Institute of General Medical Sciences through the T32 Training Grant GM099697 (RCL) and an Office of Naval Research grant N00014-06-1-0100 (MC).

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Correspondence to Raphael C. Lee.

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Maatouk, C., Ling, M., Titushkin, I. et al. Amphiphilic Block Copolymer-Catalyzed Cell Membrane Sealing Is Linked to Decreased Membrane Tension. Regen. Eng. Transl. Med. 8, 134–144 (2022).

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  • Cell membrane
  • Poration
  • Membrane tension
  • Sealing
  • Poloxamer
  • Polyethylene glycol
  • Laser optical tweezers