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Calcium and Phosphatidylserine Inhibit Lipid Electropore Formation and Reduce Pore Lifetime

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Abstract

Molecular dynamics simulations of electroporation of homogeneous phospholipid bilayers show that the pore creation time is strongly dependent on the magnitude of the applied electric field. Here, we investigated whether heterogeneous bilayers containing phospholipids with zwitterionic and anionic headgroups exhibit a similar dependence. To facilitate this analysis we divide the life cycle of an electropore into several stages, marking the sequence of steps for pore creation and pore annihilation (restoration of the bilayer after removal of the electric field). We also report simulations of calcium binding isotherms and the effects of calcium ions on the electroporation of heterogeneous lipid bilayers. Calcium binding simulations are consistent with experimental data using a 1:2 Langmuir binding isotherm. We find that calcium ions and phosphatidylserine increase pore creation time and decrease pore annihilation time. For all systems tested, pore creation time was inversely proportional to the bilayer internal electric field.

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Acknowledgements

We thank Rumiana Dimova for stimulating discussions and insightful input on calcium binding. Computing resources were provided by the USC Center for High Performance Computing and Communications (http://www.usc.edu/hpcc/). This work was made possible in part by the Air Force Office of Scientific Research and by MOSIS, Information Sciences Institute, Viterbi School of Engineering, University of Southern California.

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Correspondence to Zachary A. Levine.

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Levine, Z.A., Vernier, P.T. Calcium and Phosphatidylserine Inhibit Lipid Electropore Formation and Reduce Pore Lifetime. J Membrane Biol 245, 599–610 (2012). https://doi.org/10.1007/s00232-012-9471-1

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  • DOI: https://doi.org/10.1007/s00232-012-9471-1

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