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Cellular forces during early spreading of T lymphocytes on ultra-soft substrates

Farah Mustapha, Martine Pelicot-Biarnes, Remy Torro, Kheya Sengupta, View ORCID ProfilePierre-henri Puech
doi: https://doi.org/10.1101/2022.02.11.480084
Farah Mustapha
1Aix Marseille University, LAI UM 61, Marseille, F-13288, France
2Inserm, UMR_S 1067, Marseille, F-13288, France
3CNRS, UMR 7333, Marseille, F-13288, France
4Turing Centre for Living systems, Marseille, France
5CNRS - AMU UMR 7325, Marseille, F-13288, France
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Martine Pelicot-Biarnes
1Aix Marseille University, LAI UM 61, Marseille, F-13288, France
2Inserm, UMR_S 1067, Marseille, F-13288, France
3CNRS, UMR 7333, Marseille, F-13288, France
4Turing Centre for Living systems, Marseille, France
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Remy Torro
1Aix Marseille University, LAI UM 61, Marseille, F-13288, France
2Inserm, UMR_S 1067, Marseille, F-13288, France
3CNRS, UMR 7333, Marseille, F-13288, France
4Turing Centre for Living systems, Marseille, France
5CNRS - AMU UMR 7325, Marseille, F-13288, France
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Kheya Sengupta
4Turing Centre for Living systems, Marseille, France
5CNRS - AMU UMR 7325, Marseille, F-13288, France
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  • For correspondence: sengupta@cinam.univ-mrs.fr pierre-henri.puech@inserm.fr
Pierre-henri Puech
1Aix Marseille University, LAI UM 61, Marseille, F-13288, France
2Inserm, UMR_S 1067, Marseille, F-13288, France
3CNRS, UMR 7333, Marseille, F-13288, France
4Turing Centre for Living systems, Marseille, France
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  • ORCID record for Pierre-henri Puech
  • For correspondence: sengupta@cinam.univ-mrs.fr pierre-henri.puech@inserm.fr
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Abstract

T cells use forces to read out and act on the mechanical parameters of their microenvironment, which includes antigen presenting cells (APCs). Here we explore the early interaction of T cells with an APC-mimicking ultra-soft polymer gel exhibiting physiologically relevant stiffness in the range of 350-450 Pa. We quantify the dependence of cell spreading and stiffness on gel elasticity, and measure early time traction forces. We find that coating the surface with an antibody against the CD3 region of the TCR-complex elicits small but measurable gel deformation in the early recognition phase, which we quantify in terms of stress or energy. We show that the time evolution of the energy follows one of three distinct patterns: active fluctuation, intermittent, or sigmoidal signal. Addition of either anti-CD28 or anti-LFA1 has little impact on the total integrated energy or the maximum stress. However, the relative distribution of the energy patterns does depend on the additional ligands. Remarkably, the forces are centrifugal at very early times, and only later turn into classical in-ward pointing centripetal traction.

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Posted February 11, 2022.
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Cellular forces during early spreading of T lymphocytes on ultra-soft substrates
Farah Mustapha, Martine Pelicot-Biarnes, Remy Torro, Kheya Sengupta, Pierre-henri Puech
bioRxiv 2022.02.11.480084; doi: https://doi.org/10.1101/2022.02.11.480084
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Cellular forces during early spreading of T lymphocytes on ultra-soft substrates
Farah Mustapha, Martine Pelicot-Biarnes, Remy Torro, Kheya Sengupta, Pierre-henri Puech
bioRxiv 2022.02.11.480084; doi: https://doi.org/10.1101/2022.02.11.480084

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