IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells

Abstract Clinical use of human mesenchymal stem cells (hMSCs) is limited due to their rapid clearance, reducing their therapeutic efficacy. The inflammatory cytokine IL-1β activates hMSCs and is known to enhance their engraftment. Consequently, understanding the molecular mechanism of this inflammat...

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Autores principales:	Stephanie A. Maynard, Ekaterina Pchelintseva, Limor Zwi-Dantsis, Anika Nagelkerke, Sahana Gopal, Yuri E. Korchev, Andrew Shevchuk, Molly M. Stevens
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e49047eb91214a098278bf3e0eedaf80
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spelling	oai:doaj.org-article:e49047eb91214a098278bf3e0eedaf802021-12-02T14:02:54ZIL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells10.1038/s41598-021-86315-x2045-2322https://doaj.org/article/e49047eb91214a098278bf3e0eedaf802021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86315-xhttps://doaj.org/toc/2045-2322Abstract Clinical use of human mesenchymal stem cells (hMSCs) is limited due to their rapid clearance, reducing their therapeutic efficacy. The inflammatory cytokine IL-1β activates hMSCs and is known to enhance their engraftment. Consequently, understanding the molecular mechanism of this inflammation-triggered adhesion is of great clinical interest to improving hMSC retention at sites of tissue damage. Integrins are cell–matrix adhesion receptors, and clustering of integrins at the nanoscale underlies cell adhesion. Here, we found that IL-1β enhances adhesion of hMSCs via increased focal adhesion contacts in an α5β1 integrin-specific manner. Further, through quantitative super-resolution imaging we elucidated that IL-1β specifically increases nanoscale integrin α5β1 availability and clustering at the plasma membrane, whilst conserving cluster area. Taken together, these results demonstrate that hMSC adhesion via IL-1β stimulation is partly regulated through integrin α5β1 spatial organization at the cell surface. These results provide new insight into integrin clustering in inflammation and provide a rational basis for design of therapies directed at improving hMSC engraftment.Stephanie A. MaynardEkaterina PchelintsevaLimor Zwi-DantsisAnika NagelkerkeSahana GopalYuri E. KorchevAndrew ShevchukMolly M. StevensNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephanie A. Maynard Ekaterina Pchelintseva Limor Zwi-Dantsis Anika Nagelkerke Sahana Gopal Yuri E. Korchev Andrew Shevchuk Molly M. Stevens IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
description	Abstract Clinical use of human mesenchymal stem cells (hMSCs) is limited due to their rapid clearance, reducing their therapeutic efficacy. The inflammatory cytokine IL-1β activates hMSCs and is known to enhance their engraftment. Consequently, understanding the molecular mechanism of this inflammation-triggered adhesion is of great clinical interest to improving hMSC retention at sites of tissue damage. Integrins are cell–matrix adhesion receptors, and clustering of integrins at the nanoscale underlies cell adhesion. Here, we found that IL-1β enhances adhesion of hMSCs via increased focal adhesion contacts in an α5β1 integrin-specific manner. Further, through quantitative super-resolution imaging we elucidated that IL-1β specifically increases nanoscale integrin α5β1 availability and clustering at the plasma membrane, whilst conserving cluster area. Taken together, these results demonstrate that hMSC adhesion via IL-1β stimulation is partly regulated through integrin α5β1 spatial organization at the cell surface. These results provide new insight into integrin clustering in inflammation and provide a rational basis for design of therapies directed at improving hMSC engraftment.
format	article
author	Stephanie A. Maynard Ekaterina Pchelintseva Limor Zwi-Dantsis Anika Nagelkerke Sahana Gopal Yuri E. Korchev Andrew Shevchuk Molly M. Stevens
author_facet	Stephanie A. Maynard Ekaterina Pchelintseva Limor Zwi-Dantsis Anika Nagelkerke Sahana Gopal Yuri E. Korchev Andrew Shevchuk Molly M. Stevens
author_sort	Stephanie A. Maynard
title	IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
title_short	IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
title_full	IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
title_fullStr	IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
title_full_unstemmed	IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
title_sort	il-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e49047eb91214a098278bf3e0eedaf80
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IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells

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