IL-1β mediated nanoscale surface clustering of integrin α5β1 regulates the adhesion of mesenchymal stem cells
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2021-03-25
Date Acceptance
2021-03-10
Citation
Scientific Reports, 2021, 11 (1), pp.1-14
ISSN
2045-2322
Publisher
Nature Publishing Group
Start Page
1
End Page
14
Journal / Book Title
Scientific Reports
Volume
11
Issue
1
Copyright Statement
© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Sponsor
British Heart Foundation
Engineering & Physical Science Research Council (EPSRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Identifier
https://www.nature.com/articles/s41598-021-86315-x
Grant Number
FS/17/74/33192
EP/P011985/1
BB/M022080/1
098411/Z/12/Z
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Publication Status
Published online
Article Number
6890
Date Publish Online
2021-03-25