Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations

Abstract The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical paramet...

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Autores principales:	Esin B. Sözer, Zachary A. Levine, P. Thomas Vernier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/21c6eeaee9d24b368b451817b016cfd4
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spelling	oai:doaj.org-article:21c6eeaee9d24b368b451817b016cfd42021-12-02T11:52:29ZQuantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations10.1038/s41598-017-00092-02045-2322https://doaj.org/article/21c6eeaee9d24b368b451817b016cfd42017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00092-0https://doaj.org/toc/2045-2322Abstract The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical parameters in existing models must be replaced with physics- and biology-based terms anchored in experimental observations. We report here absolute values for the uptake of YO-PRO-1, a small-molecule fluorescent indicator of membrane integrity, into cells after a single electric pulse lasting only 6 ns. We correlate these measured values, based on fluorescence microphotometry of hundreds of individual cells, with a diffusion-based geometric analysis of pore-mediated transport and with molecular simulations of transport across electropores in a phospholipid bilayer. The results challenge the “drift and diffusion through a pore” model that dominates conventional explanatory schemes for the electroporative transfer of small molecules into cells and point to the necessity for a more complex model.Esin B. SözerZachary A. LevineP. Thomas VernierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Esin B. Sözer Zachary A. Levine P. Thomas Vernier Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations
description	Abstract The detailed molecular mechanisms underlying the permeabilization of cell membranes by pulsed electric fields (electroporation) remain obscure despite decades of investigative effort. To advance beyond descriptive schematics to the development of robust, predictive models, empirical parameters in existing models must be replaced with physics- and biology-based terms anchored in experimental observations. We report here absolute values for the uptake of YO-PRO-1, a small-molecule fluorescent indicator of membrane integrity, into cells after a single electric pulse lasting only 6 ns. We correlate these measured values, based on fluorescence microphotometry of hundreds of individual cells, with a diffusion-based geometric analysis of pore-mediated transport and with molecular simulations of transport across electropores in a phospholipid bilayer. The results challenge the “drift and diffusion through a pore” model that dominates conventional explanatory schemes for the electroporative transfer of small molecules into cells and point to the necessity for a more complex model.
format	article
author	Esin B. Sözer Zachary A. Levine P. Thomas Vernier
author_facet	Esin B. Sözer Zachary A. Levine P. Thomas Vernier
author_sort	Esin B. Sözer
title	Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations
title_short	Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations
title_full	Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations
title_fullStr	Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations
title_full_unstemmed	Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations
title_sort	quantitative limits on small molecule transport via the electropermeome — measuring and modeling single nanosecond perturbations
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/21c6eeaee9d24b368b451817b016cfd4
work_keys_str_mv	AT esinbsozer quantitativelimitsonsmallmoleculetransportviatheelectropermeomemeasuringandmodelingsinglenanosecondperturbations AT zacharyalevine quantitativelimitsonsmallmoleculetransportviatheelectropermeomemeasuringandmodelingsinglenanosecondperturbations AT pthomasvernier quantitativelimitsonsmallmoleculetransportviatheelectropermeomemeasuringandmodelingsinglenanosecondperturbations
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Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations

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