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Translocating the blood-brain barrier using electrostatics
Mammalian cell membranes regulate homeostasis, protein activity, and cell signaling. The charge at the membrane surface has been correlated with these key events. Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electros...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468918/ https://www.ncbi.nlm.nih.gov/pubmed/23087614 http://dx.doi.org/10.3389/fncel.2012.00044 |
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author | Ribeiro, Marta M. B. Domingues, Marco M. Freire, João M. Santos, Nuno C. Castanho, Miguel A. R. B. |
author_facet | Ribeiro, Marta M. B. Domingues, Marco M. Freire, João M. Santos, Nuno C. Castanho, Miguel A. R. B. |
author_sort | Ribeiro, Marta M. B. |
collection | PubMed |
description | Mammalian cell membranes regulate homeostasis, protein activity, and cell signaling. The charge at the membrane surface has been correlated with these key events. Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electrostatic interactions in pharmacokinetics and pharmacodynamics remain elusive. Recently, we reported for the first time that brain endothelial cells (EC) are more negatively charged than human umbilical cord cells, using zeta-potential measurements by dynamic light scattering. Here, we hypothesize that anionicity is a key feature of the blood-brain barrier (BBB) and contributes to select which compounds cross into the brain. For the sake of comparison, we also studied the membrane surface charge of blood components—red blood cells (RBC), platelets, and peripheral blood mononuclear cells (PBMC). To further quantitatively correlate the negative zeta-potential values with membrane charge density, model membranes with different percentages of anionic lipids were also evaluated. From all the cells tested, brain cell membranes are the most anionic and those having their lipids mostly exposed, which explains why lipophilic cationic compounds are more prone to cross the blood-brain barrier. |
format | Online Article Text |
id | pubmed-3468918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-34689182012-10-19 Translocating the blood-brain barrier using electrostatics Ribeiro, Marta M. B. Domingues, Marco M. Freire, João M. Santos, Nuno C. Castanho, Miguel A. R. B. Front Cell Neurosci Neuroscience Mammalian cell membranes regulate homeostasis, protein activity, and cell signaling. The charge at the membrane surface has been correlated with these key events. Although mammalian cells are known to be slightly anionic, quantitative information on the membrane charge and the importance of electrostatic interactions in pharmacokinetics and pharmacodynamics remain elusive. Recently, we reported for the first time that brain endothelial cells (EC) are more negatively charged than human umbilical cord cells, using zeta-potential measurements by dynamic light scattering. Here, we hypothesize that anionicity is a key feature of the blood-brain barrier (BBB) and contributes to select which compounds cross into the brain. For the sake of comparison, we also studied the membrane surface charge of blood components—red blood cells (RBC), platelets, and peripheral blood mononuclear cells (PBMC). To further quantitatively correlate the negative zeta-potential values with membrane charge density, model membranes with different percentages of anionic lipids were also evaluated. From all the cells tested, brain cell membranes are the most anionic and those having their lipids mostly exposed, which explains why lipophilic cationic compounds are more prone to cross the blood-brain barrier. Frontiers Media S.A. 2012-10-11 /pmc/articles/PMC3468918/ /pubmed/23087614 http://dx.doi.org/10.3389/fncel.2012.00044 Text en Copyright © 2012 Ribeiro, Domingues, Freire, Santos and Castanho. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Neuroscience Ribeiro, Marta M. B. Domingues, Marco M. Freire, João M. Santos, Nuno C. Castanho, Miguel A. R. B. Translocating the blood-brain barrier using electrostatics |
title | Translocating the blood-brain barrier using electrostatics |
title_full | Translocating the blood-brain barrier using electrostatics |
title_fullStr | Translocating the blood-brain barrier using electrostatics |
title_full_unstemmed | Translocating the blood-brain barrier using electrostatics |
title_short | Translocating the blood-brain barrier using electrostatics |
title_sort | translocating the blood-brain barrier using electrostatics |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468918/ https://www.ncbi.nlm.nih.gov/pubmed/23087614 http://dx.doi.org/10.3389/fncel.2012.00044 |
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