Assessing the role of surface glycans of extracellular vesicles on cellular uptake

Abstract Extracellular vesicles (EVs) are important mediators of cell-cell communication in a broad variety of physiological contexts. However, there is ambiguity around the fundamental mechanisms by which these effects are transduced, particularly in relation to their uptake by recipient cells. Mul...

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Autores principales:	Charles Williams, Raquel Pazos, Félix Royo, Esperanza González, Meritxell Roura-Ferrer, Aitor Martinez, Jorge Gamiz, Niels-Christian Reichardt, Juan M Falcón-Pérez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0505b9ca36d474d9a060675efa0f354
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spelling	oai:doaj.org-article:f0505b9ca36d474d9a060675efa0f3542021-12-02T15:09:40ZAssessing the role of surface glycans of extracellular vesicles on cellular uptake10.1038/s41598-019-48499-12045-2322https://doaj.org/article/f0505b9ca36d474d9a060675efa0f3542019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48499-1https://doaj.org/toc/2045-2322Abstract Extracellular vesicles (EVs) are important mediators of cell-cell communication in a broad variety of physiological contexts. However, there is ambiguity around the fundamental mechanisms by which these effects are transduced, particularly in relation to their uptake by recipient cells. Multiple modes of cellular entry have been suggested and we have further explored the role of glycans as potential determinants of uptake, using EVs from the murine hepatic cell lines AML12 and MLP29 as independent yet comparable models. Lectin microarray technology was employed to define the surface glycosylation patterns of EVs. Glycosidases PNGase F and neuraminidase which cleave N-glycans and terminal sialic acids, respectively, were used to analyze the relevance of these modifications to EV surface glycans on the uptake of fluorescently labelled EVs by a panel of cells representing a variety of tissues. Flow cytometry revealed an increase in affinity for EVs modified by both glycosidase treatments. High-content screening exhibited a broader range of responses with different cell types preferring different vesicle glycosylation states. We also found differences in vesicle charge after treatment with glycosidases. We conclude that glycans are key players in the tuning of EV uptake, through charge-based effects, direct glycan recognition or both, supporting glycoengineering as a toolkit for therapy development.Charles WilliamsRaquel PazosFélix RoyoEsperanza GonzálezMeritxell Roura-FerrerAitor MartinezJorge GamizNiels-Christian ReichardtJuan M Falcón-PérezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Charles Williams Raquel Pazos Félix Royo Esperanza González Meritxell Roura-Ferrer Aitor Martinez Jorge Gamiz Niels-Christian Reichardt Juan M Falcón-Pérez Assessing the role of surface glycans of extracellular vesicles on cellular uptake
description	Abstract Extracellular vesicles (EVs) are important mediators of cell-cell communication in a broad variety of physiological contexts. However, there is ambiguity around the fundamental mechanisms by which these effects are transduced, particularly in relation to their uptake by recipient cells. Multiple modes of cellular entry have been suggested and we have further explored the role of glycans as potential determinants of uptake, using EVs from the murine hepatic cell lines AML12 and MLP29 as independent yet comparable models. Lectin microarray technology was employed to define the surface glycosylation patterns of EVs. Glycosidases PNGase F and neuraminidase which cleave N-glycans and terminal sialic acids, respectively, were used to analyze the relevance of these modifications to EV surface glycans on the uptake of fluorescently labelled EVs by a panel of cells representing a variety of tissues. Flow cytometry revealed an increase in affinity for EVs modified by both glycosidase treatments. High-content screening exhibited a broader range of responses with different cell types preferring different vesicle glycosylation states. We also found differences in vesicle charge after treatment with glycosidases. We conclude that glycans are key players in the tuning of EV uptake, through charge-based effects, direct glycan recognition or both, supporting glycoengineering as a toolkit for therapy development.
format	article
author	Charles Williams Raquel Pazos Félix Royo Esperanza González Meritxell Roura-Ferrer Aitor Martinez Jorge Gamiz Niels-Christian Reichardt Juan M Falcón-Pérez
author_facet	Charles Williams Raquel Pazos Félix Royo Esperanza González Meritxell Roura-Ferrer Aitor Martinez Jorge Gamiz Niels-Christian Reichardt Juan M Falcón-Pérez
author_sort	Charles Williams
title	Assessing the role of surface glycans of extracellular vesicles on cellular uptake
title_short	Assessing the role of surface glycans of extracellular vesicles on cellular uptake
title_full	Assessing the role of surface glycans of extracellular vesicles on cellular uptake
title_fullStr	Assessing the role of surface glycans of extracellular vesicles on cellular uptake
title_full_unstemmed	Assessing the role of surface glycans of extracellular vesicles on cellular uptake
title_sort	assessing the role of surface glycans of extracellular vesicles on cellular uptake
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/f0505b9ca36d474d9a060675efa0f354
work_keys_str_mv	AT charleswilliams assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT raquelpazos assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT felixroyo assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT esperanzagonzalez assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT meritxellrouraferrer assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT aitormartinez assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT jorgegamiz assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT nielschristianreichardt assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake AT juanmfalconperez assessingtheroleofsurfaceglycansofextracellularvesiclesoncellularuptake
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Assessing the role of surface glycans of extracellular vesicles on cellular uptake

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