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Imaging CD4 T Cell Interstitial Migration in the Inflamed Dermis
Published on: March 25, 2016
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Immune cells employ intermittent integrin-mediated traction forces for 3D migration
Tina Czerwinski1, Lars Bischof1, David Böhringer1
1Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen 91058, Germany.
Summary
Immune cells, like natural killer (NK) cells, can switch migration modes to navigate dense tissues. This adaptability helps them overcome physical barriers by employing contractile forces when needed.
Area of Science:
- Cellular Biology
- Immunology
- Biophysics
Background:
- Immune cells migrate through tissues to reach targets, typically using an amoeboid motion.
- The mechanism by which immune cells overcome steric hindrance in dense matrices during migration is not fully understood.
- Amoeboid migration is characterized by speed but may be insufficient for navigating complex tissue architectures.
Purpose of the Study:
- To investigate how immune cells adapt their migration strategies in dense, fibrous tissues.
- To elucidate the role of cell contractility and adhesion in overcoming steric hindrance during immune cell infiltration.
- To identify the cellular mechanisms enabling immune cell navigation through challenging microenvironments.
Main Methods:
- Utilized natural killer (NK92) cells and primary immune cells (B, T, NK cells, neutrophils, monocytes).
- Studied cell migration in fibrous human amniotic membrane (HAM) tissue and reconstituted 3D collagen networks.
- Employed time-lapse confocal reflection microscopy for simultaneous measurement of migration speed, persistence, and cell contractility.
Main Results:
- NK92 cells switch from amoeboid to a contractile, mesenchymal-like migration mode in dense HAM tissue.
- Immune cells generate acto-myosin driven, integrin-mediated contractile forces (up to 100 nN) during migration bursts.
- This contractile behavior correlates with cells becoming trapped in narrow matrix pores, observed across multiple immune cell types.
Conclusions:
- Immune cells exhibit a remarkable plasticity in migration modes, adapting to tissue density and physical constraints.
- Steric hindrance in dense matrices triggers rapid regulation of integrin-mediated adhesion and cell contractility.
- This adaptive migration strategy is crucial for effective immune cell infiltration and function across various immune cell subtypes.
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