Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses
Science increasingly involves complex modeling. Here we describe a model for cell electroporation in which membrane properties are dynamically modified by poration. Spatial scales range from cell membrane thickness (5 nm) to a typical mammalian cell radius (10 μ m), and can be used with idealized a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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Springer Science+Business Media
2015
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| Online Access: | http://hdl.handle.net/1721.1/96516 https://orcid.org/0000-0002-9016-5962 |
| _version_ | 1811082088317714432 |
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| author | Son, Reuben S. Smith, Kyle C. Gowrishankar, Thiruvallur R. Vernier, P. Thomas Weaver, James C. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Son, Reuben S. Smith, Kyle C. Gowrishankar, Thiruvallur R. Vernier, P. Thomas Weaver, James C. |
| author_sort | Son, Reuben S. |
| collection | MIT |
| description | Science increasingly involves complex modeling. Here we describe a model for cell electroporation in which membrane properties are dynamically modified by poration. Spatial scales range from cell membrane thickness (5 nm) to a typical mammalian cell radius (10 μ m), and can be used with idealized and experimental pulse waveforms. The model consists of traditional passive components and additional active components representing nonequilibrium processes. Model responses include measurable quantities: transmembrane voltage, membrane electrical conductance, and solute transport rates and amounts for the representative “long” and “short” pulses. The long pulse—1.5 kV/cm, 100 μ s—evolves two pore subpopulations with a valley at ∼ 5 nm, which separates the subpopulations that have peaks at ∼ 1.5 and ∼ 12 nm radius. Such pulses are widely used in biological research, biotechnology, and medicine, including cancer therapy by drug delivery and nonthermal physical tumor ablation by causing necrosis. The short pulse—40 kV/cm, 10 ns—creates 80-fold more pores, all small ( < 3 nm; ∼ 1 nm peak). These nanosecond pulses ablate tumors by apoptosis. We demonstrate the model’s responses by illustrative electrical and poration behavior, and transport of calcein and propidium. We then identify extensions for expanding modeling capability. Structure-function results from MD can allow extrapolations that bring response specificity to cell membranes based on their lipid composition. After a pulse, changes in pore energy landscape can be included over seconds to minutes, by mechanisms such as cell swelling and pulse-induced chemical reactions that slowly alter pore behavior. |
| first_indexed | 2024-09-23T11:57:23Z |
| format | Article |
| id | mit-1721.1/96516 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:57:23Z |
| publishDate | 2015 |
| publisher | Springer Science+Business Media |
| record_format | dspace |
| spelling | mit-1721.1/965162024-03-20T19:29:10Z Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses Son, Reuben S. Smith, Kyle C. Gowrishankar, Thiruvallur R. Vernier, P. Thomas Weaver, James C. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Son, Reuben S. Smith, Kyle C. Gowrishankar, Thiruvallur R. Weaver, James C. Science increasingly involves complex modeling. Here we describe a model for cell electroporation in which membrane properties are dynamically modified by poration. Spatial scales range from cell membrane thickness (5 nm) to a typical mammalian cell radius (10 μ m), and can be used with idealized and experimental pulse waveforms. The model consists of traditional passive components and additional active components representing nonequilibrium processes. Model responses include measurable quantities: transmembrane voltage, membrane electrical conductance, and solute transport rates and amounts for the representative “long” and “short” pulses. The long pulse—1.5 kV/cm, 100 μ s—evolves two pore subpopulations with a valley at ∼ 5 nm, which separates the subpopulations that have peaks at ∼ 1.5 and ∼ 12 nm radius. Such pulses are widely used in biological research, biotechnology, and medicine, including cancer therapy by drug delivery and nonthermal physical tumor ablation by causing necrosis. The short pulse—40 kV/cm, 10 ns—creates 80-fold more pores, all small ( < 3 nm; ∼ 1 nm peak). These nanosecond pulses ablate tumors by apoptosis. We demonstrate the model’s responses by illustrative electrical and poration behavior, and transport of calcein and propidium. We then identify extensions for expanding modeling capability. Structure-function results from MD can allow extrapolations that bring response specificity to cell membranes based on their lipid composition. After a pulse, changes in pore energy landscape can be included over seconds to minutes, by mechanisms such as cell swelling and pulse-induced chemical reactions that slowly alter pore behavior. Harvard University--MIT Division of Health Sciences and Technology (Fellowship) National Science Foundation (U.S.) (Fellowship) National Institutes of Health (U.S.) (NIH grant GM063857) United States. Air Force Office of Scientific Research University of Southern California. Center for High Performance Computing and Communications 2015-04-10T14:24:19Z 2015-04-10T14:24:19Z 2014-07 2014-04 Article http://purl.org/eprint/type/JournalArticle 0022-2631 1432-1424 http://hdl.handle.net/1721.1/96516 Son, Reuben S., Kyle C. Smith, Thiruvallur R. Gowrishankar, P. Thomas Vernier, and James C. Weaver. “Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses.” J Membrane Biol 247, no. 12 (July 22, 2014): 1209–1228. https://orcid.org/0000-0002-9016-5962 en_US http://dx.doi.org/10.1007/s00232-014-9699-z http://hdl.handle.net/1721.1/97734 http://hdl.handle.net/1721.1/97707 Journal of Membrane Biology Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science+Business Media Springer-Verlag |
| spellingShingle | Son, Reuben S. Smith, Kyle C. Gowrishankar, Thiruvallur R. Vernier, P. Thomas Weaver, James C. Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses |
| title | Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses |
| title_full | Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses |
| title_fullStr | Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses |
| title_full_unstemmed | Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses |
| title_short | Basic Features of a Cell Electroporation Model: Illustrative Behavior for Two Very Different Pulses |
| title_sort | basic features of a cell electroporation model illustrative behavior for two very different pulses |
| url | http://hdl.handle.net/1721.1/96516 https://orcid.org/0000-0002-9016-5962 |
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