Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors

Abstract Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via ind...

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Autores principales:	Marta Targosz-Korecka, Agata Kubisiak, Damian Kloska, Aleksandra Kopacz, Anna Grochot-Przeczek, Marek Szymonski
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ca3b52fc1b24a2a99f151a75250728c
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spelling	oai:doaj.org-article:8ca3b52fc1b24a2a99f151a75250728c2021-12-02T17:47:04ZEndothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors10.1038/s41598-021-91231-12045-2322https://doaj.org/article/8ca3b52fc1b24a2a99f151a75250728c2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91231-1https://doaj.org/toc/2045-2322Abstract Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.Marta Targosz-KoreckaAgata KubisiakDamian KloskaAleksandra KopaczAnna Grochot-PrzeczekMarek SzymonskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marta Targosz-Korecka Agata Kubisiak Damian Kloska Aleksandra Kopacz Anna Grochot-Przeczek Marek Szymonski Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
description	Abstract Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.
format	article
author	Marta Targosz-Korecka Agata Kubisiak Damian Kloska Aleksandra Kopacz Anna Grochot-Przeczek Marek Szymonski
author_facet	Marta Targosz-Korecka Agata Kubisiak Damian Kloska Aleksandra Kopacz Anna Grochot-Przeczek Marek Szymonski
author_sort	Marta Targosz-Korecka
title	Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
title_short	Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
title_full	Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
title_fullStr	Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
title_full_unstemmed	Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors
title_sort	endothelial glycocalyx shields the interaction of sars-cov-2 spike protein with ace2 receptors
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ca3b52fc1b24a2a99f151a75250728c
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Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors

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