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T-cell activation is modulated by the 3D mechanical microenvironment

Fatemeh S. Majedi, Mohammad Mahdi Hasani-Sadrabadi, Timothy J. Thauland, Song Li, Louis-S. Bouchard, Manish J. Butte
doi: https://doi.org/10.1101/580886
Fatemeh S. Majedi
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Mohammad Mahdi Hasani-Sadrabadi
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Timothy J. Thauland
2Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Song Li
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Louis-S. Bouchard
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095 USA
3Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Manish J. Butte
2Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, 90095 USA
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Abstract

T cells recognize mechanical forces through a variety of cellular pathways, including mechanical triggering of the T-cell receptor (TCR) and mechanical triggering of the integrin LFA-1. We show here that T cells can recognize forces arising from the rigidity of the microenvironment. We fabricated 3D hydrogels with mechanical stiffness tuned to 4 kPa and 40 kPa and specially engineered be microporous independent of stiffness. We cultured T cells and antigen presenting cells within the matrices and studied activation by flow cytometry and live imaging. We found there was an augmentation of T-cell activation in the context of mechanically stiffer 3D material as compared to the softer material. In contrast, proliferation, activation markers, and migration were all diminished in T cells cultured in the softer material. These results show that T cells can sense their mechanical environment and amplify responses in the context of mechanical stiffness.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 18, 2019.
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T-cell activation is modulated by the 3D mechanical microenvironment
Fatemeh S. Majedi, Mohammad Mahdi Hasani-Sadrabadi, Timothy J. Thauland, Song Li, Louis-S. Bouchard, Manish J. Butte
bioRxiv 580886; doi: https://doi.org/10.1101/580886
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T-cell activation is modulated by the 3D mechanical microenvironment
Fatemeh S. Majedi, Mohammad Mahdi Hasani-Sadrabadi, Timothy J. Thauland, Song Li, Louis-S. Bouchard, Manish J. Butte
bioRxiv 580886; doi: https://doi.org/10.1101/580886

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