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Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
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Agonist leukadherin-1 increases CD11b/CD18-dependent adhesion via membrane tethers
Emrah Celik1, Mohd Hafeez Faridi, Vinay Kumar
1Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida.
Biophysical Journal
|December 10, 2013
Summary
Leukadherin-1 (LA1) enhances leukocyte adhesion by promoting membrane tether bonds, while Mn(2+) strengthens cytoskeleton-anchored bonds. This reveals distinct integrin activation mechanisms for cell adhesion and immune response.
Area of Science:
- Biophysics
- Cellular Biology
- Immunology
Background:
- Integrin CD11b/CD18 is crucial for leukocyte migration and immune responses.
- Leukadherin-1 (LA1) is a small molecule that boosts CD11b/CD18-mediated cell adhesion to ICAM-1.
Purpose of the Study:
- To investigate the biophysical mechanism of LA1-activated CD11b/CD18 in leukocyte adhesion.
- To differentiate the binding mechanisms of LA1 and Mn(2+) in integrin activation.
Main Methods:
- Single-molecule force spectroscopy was employed.
- Atomic force microscopy was used to analyze cell detachment forces and distances.
Main Results:
- LA1 enhanced CD11b/CD18 binding to ICAM-1 through long membrane tethers.
- Mn(2+) increased ICAM-1 binding via cytoskeleton-anchored bonds.
- LA1-activated neutrophils showed longer detachment but lower force compared to Mn(2+)-activated cells.
Conclusions:
- LA1 and Mn(2+) differentially activate integrins and couple them to cellular machinery.
- These findings offer new insights into signal mechanotransduction by integrin agonists.
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