The Force-Dependent Mechanism of an Integrin α4β7-MAdCAM-1 Interaction.
Youmin SuZhiqing LuoDongshan SunBishan YangQuhuan LiPublished in: International journal of molecular sciences (2023)
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 2+ and/or Mg 2+ 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 2+ rather than Ca 2+ . 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.
Keyphrases
- cell adhesion
- cell migration
- single molecule
- atomic force microscopy
- induced apoptosis
- biofilm formation
- oxidative stress
- cell cycle arrest
- gene expression
- magnetic resonance imaging
- cancer therapy
- drug delivery
- staphylococcus aureus
- genome wide
- pseudomonas aeruginosa
- cystic fibrosis
- ulcerative colitis
- high resolution
- protein kinase
- candida albicans
- pi k akt
- transition metal