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Functional Mapping of Adhesiveness on Live Cells Reveals How Guidance Phenotypes Can Emerge From Complex
Philippe Robert1, Martine Biarnes-Pelicot1, Nicolas Garcia-Seyda1
1LAI, Aix-Marseille University, CNRS, INSERM U1067 Adhésion Cellulaires et lnflammation, Turing Center for Living Systems, Marseille, France.
Frontiers in Bioengineering and Biotechnology
|April 26, 2021
Summary
Scientists developed a new method to measure cell adhesion on live immune cells, revealing how integrins guide T lymphocyte movement. This study maps integrin adhesiveness, uncovering signaling crosstalk crucial for cell guidance.
Area of Science:
- Cell Biology
- Immunology
- Biophysics
Background:
- Immune cells require adaptable adhesiveness for migration, mediated by integrins.
- Probing cell adhesion on live, motile cells without disruption is a significant challenge.
Purpose of the Study:
- To develop a novel in vitro method for probing local surface adhesiveness of live, motile cells.
- To functionally map integrin-mediated adhesiveness on human T lymphocytes.
- To investigate the spatiotemporal regulation of integrin-mediated adhesiveness.
Main Methods:
- Developed a novel in vitro method using flow-pulled micron-size beads to probe cell surface adhesiveness.
- Functional mapping of VLA-4 and LFA-1 integrin adhesiveness on live human T lymphocytes.
- Quantitative 3D immunostaining and molecular imaging combined with functional assays.
Main Results:
- Cell polarization enhances integrin adhesiveness at the cell rear (VLA-4) and front (LFA-1).
- Discovered inhibitory crosstalk of LFA-1 on VLA-4 and activating crosstalk of VLA-4 on LFA-1.
- Identified high-affinity integrin densities and revealed latent adhesiveness not detected by immunostaining.
Conclusions:
- The novel bead-based assay effectively probes live cell adhesiveness, complementing traditional methods.
- Integrin crosstalk and polarization-dependent adhesiveness are critical for T lymphocyte guidance under flow.
- This approach provides new insights into the regulation of cell motility and guidance.
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