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Engineered Trehalose Permeable to Mammalian Cells

Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freez...

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Autores principales: Abazari, Alireza, Meimetis, Labros G., Budin, Ghyslain, Bale, Shyam Sundhar, Weissleder, Ralph, Toner, Mehmet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482662/
https://www.ncbi.nlm.nih.gov/pubmed/26115179
http://dx.doi.org/10.1371/journal.pone.0130323
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author Abazari, Alireza
Meimetis, Labros G.
Budin, Ghyslain
Bale, Shyam Sundhar
Weissleder, Ralph
Toner, Mehmet
author_facet Abazari, Alireza
Meimetis, Labros G.
Budin, Ghyslain
Bale, Shyam Sundhar
Weissleder, Ralph
Toner, Mehmet
author_sort Abazari, Alireza
collection PubMed
description Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre) demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre) and trehalose tetraacetate (4-O-Ac-Tre). Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants) reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies.
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spelling pubmed-44826622015-06-29 Engineered Trehalose Permeable to Mammalian Cells Abazari, Alireza Meimetis, Labros G. Budin, Ghyslain Bale, Shyam Sundhar Weissleder, Ralph Toner, Mehmet PLoS One Research Article Trehalose is a naturally occurring disaccharide which is associated with extraordinary stress-tolerance capacity in certain species of unicellular and multicellular organisms. In mammalian cells, presence of intra- and extracellular trehalose has been shown to confer improved tolerance against freezing and desiccation. Since mammalian cells do not synthesize nor import trehalose, the development of novel methods for efficient intracellular delivery of trehalose has been an ongoing investigation. Herein, we studied the membrane permeability of engineered lipophilic derivatives of trehalose. Trehalose conjugated with 6 acetyl groups (trehalose hexaacetate or 6-O-Ac-Tre) demonstrated superior permeability in rat hepatocytes compared with regular trehalose, trehalose diacetate (2-O-Ac-Tre) and trehalose tetraacetate (4-O-Ac-Tre). Once in the cell, intracellular esterases hydrolyzed the 6-O-Ac-Tre molecules, releasing free trehalose into the cytoplasm. The total concentration of intracellular trehalose (plus acetylated variants) reached as high as 10 fold the extracellular concentration of 6-O-Ac-Tre, attaining concentrations suitable for applications in biopreservation. To describe this accumulation phenomenon, a diffusion-reaction model was proposed and the permeability and reaction kinetics of 6-O-Ac-Tre were determined by fitting to experimental data. Further studies suggested that the impact of the loading and the presence of intracellular trehalose on cellular viability and function were negligible. Engineering of trehalose chemical structure rather than manipulating the cell, is an innocuous, cell-friendly method for trehalose delivery, with demonstrated potential for trehalose loading in different types of cells and cell lines, and can facilitate the wide-spread application of trehalose as an intracellular protective agent in biopreservation studies. Public Library of Science 2015-06-26 /pmc/articles/PMC4482662/ /pubmed/26115179 http://dx.doi.org/10.1371/journal.pone.0130323 Text en © 2015 Abazari et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Abazari, Alireza
Meimetis, Labros G.
Budin, Ghyslain
Bale, Shyam Sundhar
Weissleder, Ralph
Toner, Mehmet
Engineered Trehalose Permeable to Mammalian Cells
title Engineered Trehalose Permeable to Mammalian Cells
title_full Engineered Trehalose Permeable to Mammalian Cells
title_fullStr Engineered Trehalose Permeable to Mammalian Cells
title_full_unstemmed Engineered Trehalose Permeable to Mammalian Cells
title_short Engineered Trehalose Permeable to Mammalian Cells
title_sort engineered trehalose permeable to mammalian cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482662/
https://www.ncbi.nlm.nih.gov/pubmed/26115179
http://dx.doi.org/10.1371/journal.pone.0130323
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