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Heterogeneity of single-cell mechanical responses to tumorigenic factors

Aldo Leal-Egaña, Gaelle Letort, Jean-Louis Martiel, Andreas Christ, Timothée Vignaud, Caroline Roelants, Odile Filhol, Manuel Théry
doi: https://doi.org/10.1101/078154
Aldo Leal-Egaña
CytoMorpho Lab, LPCV, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CEA, CNRS, INRA, Université Grenoble-Alpes, Grenoble, France.
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Gaelle Letort
CytoMorpho Lab, LPCV, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CEA, CNRS, INRA, Université Grenoble-Alpes, Grenoble, France.
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Jean-Louis Martiel
CytoMorpho Lab, LPCV, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CEA, CNRS, INRA, Université Grenoble-Alpes, Grenoble, France.
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Andreas Christ
CytoMorpho Lab, LPCV, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CEA, CNRS, INRA, Université Grenoble-Alpes, Grenoble, France.
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Timothée Vignaud
CytoMorpho Lab, LPCV, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CEA, CNRS, INRA, Université Grenoble-Alpes, Grenoble, France.
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Caroline Roelants
Biologie du Cancer et de l’Infection, Biosciences & Biotechnology Institute of Grenoble, UMRS1036, CEA, INSERM, CNRS, Université Grenoble-Alpes, Grenoble, France.
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Odile Filhol
Biologie du Cancer et de l’Infection, Biosciences & Biotechnology Institute of Grenoble, UMRS1036, CEA, INSERM, CNRS, Université Grenoble-Alpes, Grenoble, France.
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Manuel Théry
CytoMorpho Lab, LPCV, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CEA, CNRS, INRA, Université Grenoble-Alpes, Grenoble, France.CytoMorpho Lab, A2T, Hopital Saint Louis, Institut Universitaire d’Hematologie, UMRS1160, CEA, INSERM, AP-HP, Université Paris Diderot, Paris, France.
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Abstract

Tumor development progresses through a complex path of biomechanical changes leading first to cell growth and contraction followed by cell de-adhesion, scattering and invasion. Tumorigenic factors may act specifically on one of these steps or have wider spectrum of actions, leading to a variety of effects and thus sometimes to apparent contradictory outcomes. Here we used micropatterned lines of collagen type-I/fibronectin on deformable surfaces to standardize cell behavior and to measure simultaneously cell size, speed of motion and the magnitude of the associated contractile forces at the level of a single cell. We analyzed and compared normal human breast cell line MCF10A in control conditions and in response to various tumorigenic factors. In all conditions, distinct populations of cells with a wide range of biomechanical properties were identified. Despite this heterogeneity, normal and transformed motile cells followed a common trend whereby size and contractile forces were negatively correlated with cell speed. Some tumorigenic factors, such as activation of ErbB2 or the loss of the beta subunit of casein kinase 2 (CK2), shifted the whole population towards a faster speed and lower contractility state. Treatment with transforming growth factor beta (TGF-β), induced some cells to adopt opposing behaviors such as extreme high contractility versus extreme low contractility. Thus, tumor transformation amplified the pre-existing population heterogeneity and led some cells to exhibit biomechanical properties that were more extreme than that observed with normal cells.

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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 September 30, 2016.
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Heterogeneity of single-cell mechanical responses to tumorigenic factors
Aldo Leal-Egaña, Gaelle Letort, Jean-Louis Martiel, Andreas Christ, Timothée Vignaud, Caroline Roelants, Odile Filhol, Manuel Théry
bioRxiv 078154; doi: https://doi.org/10.1101/078154
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Heterogeneity of single-cell mechanical responses to tumorigenic factors
Aldo Leal-Egaña, Gaelle Letort, Jean-Louis Martiel, Andreas Christ, Timothée Vignaud, Caroline Roelants, Odile Filhol, Manuel Théry
bioRxiv 078154; doi: https://doi.org/10.1101/078154

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