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  • Technical Review
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Measuring mechanical stress in living tissues

Abstract

Living tissues are active, multifunctional materials capable of generating, sensing, withstanding and responding to mechanical stress. These capabilities enable tissues to adopt complex shapes during development, to sustain those shapes during homeostasis and to restore them during healing and regeneration. Abnormal stress is associated with a broad range of pathological conditions, including developmental defects, inflammatory diseases, tumour growth and metastasis. A number of techniques are available to measure mechanical stress in living tissues at cellular and subcellular resolution. 2D techniques that map stress in cultured cell monolayers provide the highest resolution and accessibility, and include 2D traction force microscopy, micropillar arrays, monolayer stress microscopy and monolayer stretching between flexible cantilevers. Mapping stresses in tissues cultured in 3D can be achieved using 3D traction force microscopy and the microbulge test. Techniques for measuring stress in vivo include servo-null methods for measuring luminal pressure, deformable inclusions, Förster resonance energy transfer tension sensors, laser ablation and computational methods for force inference. Although these techniques are far from becoming everyday tools in biomedical laboratories, their rapid development is fostering key advances in our understanding of the role of mechanics in morphogenesis, homeostasis and disease.

Key points

  • Mechanical stresses generated by cells determine the fate, form and function of living tissues.

  • Several techniques have been developed to measure tissue stress at subcellular resolution.

  • State-of-the-art technologies now enable high-resolution mapping of time-varying stress fields in 2D and 3D cell cultures.

  • Measuring stresses in vivo remains an outstanding challenge that is currently addressed through the combination of image-based computational modelling and the insertion of soft inclusions in tissues of interest.

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Fig. 1: Techniques for measuring tractions and internal stresses in 2D tissues in vitro.
Fig. 2: Techniques for measuring tractions and internal stresses in 3D tissues in vitro.
Fig. 3: Techniques for measuring internal stresses in vivo.

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Acknowledgements

The authors apologize to the many colleagues whose work could not be cited owing to space constraints. The authors thank N. Grummel, D. Böhringer and B. Fabry for providing Fig. 2d, and A. Marin-Llauradó and T. Golde for critical reading of the manuscript. The authors are funded by the Spanish Ministry of Science, Innovation and Universities MICINN/FEDER (PGC2018-099645-B-I00 to X.T., DPI2015-71789-R to M.A.), the Generalitat de Catalunya (2017-FI-B1-00068 grant to E.L., SGR-2017-01602 grant to X.T. and 2014-SGR-1471 grant to M.A.), the CERCA Programme and ICREA Academia award (to M.A.), the European Research Council (grant CoG-616480 to X.T. and grant CoG-681434 to M.A.), the European Union’s Horizon 2020 research and innovation programme (under the Marie Skłodowska-Curie grant agreement no. 797621 to M.G.-G.), Obra Social “la Caixa” and Fundació la Marató de TV3 (project 201903-30-31-32 to X.T.). The IBEC is the recipient of a Severo Ochoa Award of Excellence from the Spanish Ministry of Economy and Competitiveness (MINECO).

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Gómez-González, M., Latorre, E., Arroyo, M. et al. Measuring mechanical stress in living tissues. Nat Rev Phys 2, 300–317 (2020). https://doi.org/10.1038/s42254-020-0184-6

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