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

Abstract

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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Acknowledgements

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

Funding

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). https://doi.org/10.1007/s40883-021-00206-1

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  • DOI: https://doi.org/10.1007/s40883-021-00206-1

Keywords

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