The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 Interaction
The interaction between integrin α4β7 and mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1) facilitates the adhesion of circulating lymphocytes to the surface of high endothelial venules in inflammatory bowel diseases (IBDs). Lymphocyte adhesion is a multistep cascade involving the teth...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16062 |
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| author | Youmin Su Zhiqing Luo Dongshan Sun Bishan Yang Quhuan Li |
| author_facet | Youmin Su Zhiqing Luo Dongshan Sun Bishan Yang Quhuan Li |
| author_sort | Youmin Su |
| collection | DOAJ |
| description | The interaction between integrin α4β7 and mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1) facilitates the adhesion of circulating lymphocytes to the surface of high endothelial venules in inflammatory bowel diseases (IBDs). Lymphocyte adhesion is a multistep cascade involving the tethering, rolling, stable adhesion, crawling, and migration of cells, with integrin α4β7 being involved in rolling and stable adhesions. Targeting the integrin α4β7–MAdCAM-1 interaction may help decrease inflammation in IBDs. This interaction is regulated by force; however, the underlying mechanism remains unknown. Here, we investigate this mechanism using a parallel plate flow chamber and atomic force microscopy. The results reveal an initial increase in the lifetime of the integrin α4β7–MAdCAM-1 interaction followed by a decrease with an increasing force. This was manifested in a two-state curve regulated via a catch-bond–slip-bond conversion regardless of Ca<sup>2+</sup> and/or Mg<sup>2+</sup> availability. In contrast, the mean rolling velocity of cells initially decreased and then increased with the increasing force, indicating the flow-enhanced adhesion. Longer tether lifetimes of single bonds and lower rolling velocities mediated by multiple bonds were observed in the presence of Mg<sup>2+</sup> rather than Ca<sup>2+</sup>. Similar results were obtained when examining the adhesion to substrates co-coated with chemokine CC motif ligand 25 and MAdCAM-1, as opposed to substrates coated with MAdCAM-1 alone. In conclusion, the integrin α4β7–MAdCAM-1 interaction occurs via ion- and cytokine-dependent flow-enhanced adhesion processes and is regulated via a catch-bond mechanism. |
| first_indexed | 2024-03-09T16:46:59Z |
| format | Article |
| id | doaj.art-6d7fea5c1efb4026847a10cb6baffaa2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:46:59Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6d7fea5c1efb4026847a10cb6baffaa22023-11-24T14:45:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221606210.3390/ijms242216062The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 InteractionYoumin Su0Zhiqing Luo1Dongshan Sun2Bishan Yang3Quhuan Li4School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, ChinaThe interaction between integrin α4β7 and mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1) facilitates the adhesion of circulating lymphocytes to the surface of high endothelial venules in inflammatory bowel diseases (IBDs). Lymphocyte adhesion is a multistep cascade involving the tethering, rolling, stable adhesion, crawling, and migration of cells, with integrin α4β7 being involved in rolling and stable adhesions. Targeting the integrin α4β7–MAdCAM-1 interaction may help decrease inflammation in IBDs. This interaction is regulated by force; however, the underlying mechanism remains unknown. Here, we investigate this mechanism using a parallel plate flow chamber and atomic force microscopy. The results reveal an initial increase in the lifetime of the integrin α4β7–MAdCAM-1 interaction followed by a decrease with an increasing force. This was manifested in a two-state curve regulated via a catch-bond–slip-bond conversion regardless of Ca<sup>2+</sup> and/or Mg<sup>2+</sup> availability. In contrast, the mean rolling velocity of cells initially decreased and then increased with the increasing force, indicating the flow-enhanced adhesion. Longer tether lifetimes of single bonds and lower rolling velocities mediated by multiple bonds were observed in the presence of Mg<sup>2+</sup> rather than Ca<sup>2+</sup>. Similar results were obtained when examining the adhesion to substrates co-coated with chemokine CC motif ligand 25 and MAdCAM-1, as opposed to substrates coated with MAdCAM-1 alone. In conclusion, the integrin α4β7–MAdCAM-1 interaction occurs via ion- and cytokine-dependent flow-enhanced adhesion processes and is regulated via a catch-bond mechanism.https://www.mdpi.com/1422-0067/24/22/16062integrin α4β7MAdCAM-1flow-enhanced adhesioncatch bond |
| spellingShingle | Youmin Su Zhiqing Luo Dongshan Sun Bishan Yang Quhuan Li The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 Interaction International Journal of Molecular Sciences integrin α4β7 MAdCAM-1 flow-enhanced adhesion catch bond |
| title | The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 Interaction |
| title_full | The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 Interaction |
| title_fullStr | The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 Interaction |
| title_full_unstemmed | The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 Interaction |
| title_short | The Force-Dependent Mechanism of an Integrin α4β7–MAdCAM-1 Interaction |
| title_sort | force dependent mechanism of an integrin α4β7 madcam 1 interaction |
| topic | integrin α4β7 MAdCAM-1 flow-enhanced adhesion catch bond |
| url | https://www.mdpi.com/1422-0067/24/22/16062 |
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