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Optogenetic control of cellular forces and mechanotransduction

Author

Listed:
  • Léo Valon

    (Institute for Bioengineering of Catalonia)

  • Ariadna Marín-Llauradó

    (Institute for Bioengineering of Catalonia)

  • Thomas Wyatt

    (MRC Laboratory for Molecular Cell Biology, University College London
    London Centre for Nanotechnology)

  • Guillaume Charras

    (London Centre for Nanotechnology
    University College London)

  • Xavier Trepat

    (Institute for Bioengineering of Catalonia
    Facultat de Medicina, Universitat de Barcelona
    Institució Catalana de Recerca i Estudis Avançats (ICREA)
    Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina)

Abstract

Contractile forces are the end effectors of cell migration, division, morphogenesis, wound healing and cancer invasion. Here we report optogenetic tools to upregulate and downregulate such forces with high spatiotemporal accuracy. The technology relies on controlling the subcellular activation of RhoA using the CRY2/CIBN light-gated dimerizer system. We fused the catalytic domain (DHPH domain) of the RhoA activator ARHGEF11 to CRY2-mCherry (optoGEF-RhoA) and engineered its binding partner CIBN to bind either to the plasma membrane or to the mitochondrial membrane. Translocation of optoGEF-RhoA to the plasma membrane causes a rapid and local increase in cellular traction, intercellular tension and tissue compaction. By contrast, translocation of optoGEF-RhoA to mitochondria results in opposite changes in these physical properties. Cellular changes in contractility are paralleled by modifications in the nuclear localization of the transcriptional regulator YAP, thus showing the ability of our approach to control mechanotransductory signalling pathways in time and space.

Suggested Citation

  • Léo Valon & Ariadna Marín-Llauradó & Thomas Wyatt & Guillaume Charras & Xavier Trepat, 2017. "Optogenetic control of cellular forces and mechanotransduction," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14396
    DOI: 10.1038/ncomms14396
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    Cited by:

    1. Yuqi Zhang & Yizeng Li & Keyata N. Thompson & Konstantin Stoletov & Qinling Yuan & Kaustav Bera & Se Jong Lee & Runchen Zhao & Alexander Kiepas & Yao Wang & Panagiotis Mistriotis & Selma A. Serra & Jo, 2022. "Polarized NHE1 and SWELL1 regulate migration direction, efficiency and metastasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Guillermo Martínez-Ara & Núria Taberner & Mami Takayama & Elissavet Sandaltzopoulou & Casandra E. Villava & Miquel Bosch-Padrós & Nozomu Takata & Xavier Trepat & Mototsugu Eiraku & Miki Ebisuya, 2022. "Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Kei Yamamoto & Haruko Miura & Motohiko Ishida & Yusuke Mii & Noriyuki Kinoshita & Shinji Takada & Naoto Ueno & Satoshi Sawai & Yohei Kondo & Kazuhiro Aoki, 2021. "Optogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Ariadna Marín-Llauradó & Sohan Kale & Adam Ouzeri & Tom Golde & Raimon Sunyer & Alejandro Torres-Sánchez & Ernest Latorre & Manuel Gómez-González & Pere Roca-Cusachs & Marino Arroyo & Xavier Trepat, 2023. "Mapping mechanical stress in curved epithelia of designed size and shape," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Adrien Méry & Artur Ruppel & Jean Revilloud & Martial Balland & Giovanni Cappello & Thomas Boudou, 2023. "Light-driven biological actuators to probe the rheology of 3D microtissues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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