Abstract
Mechanical homeostasis—a fundamental process by which cells maintain stable states under environmental perturbations—is regulated by two subcellular mechanotransducers: cytoskeleton tension and integrin-mediated focal adhesions (FAs)1,2,3,4,5. Here, we show that single-cell mechanical homeostasis is collectively driven by the distinct, graduated dynamics (rheostasis) of subcellular cytoskeleton tension and FAs. Such rheostasis involves a mechanosensitive pattern wherein ground states of cytoskeleton tension and FA determine their distinct reactive paths through either relaxation or reinforcement. Pharmacological perturbations of the cytoskeleton and molecularly modulated integrin catch–slip bonds biased the rheostasis and induced non-homeostasis of FAs, but not of cytoskeleton tension, suggesting a unique sensitivity of FAs in regulating homeostasis. Theoretical modelling revealed myosin-mediated cytoskeleton contractility and catch–slip-bond-like behaviours in FAs and the cytoskeleton as sufficient and necessary mechanisms for quantitatively recapitulating mechanosensitive rheostasis. Our findings highlight the previously underappreciated physical nature of the mechanical homeostasis of cells.
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Acknowledgements
We thank A. Bershadsky for providing REF-52 cells, G. J. Fisher for providing human skin fibroblasts, and A. Liu for comments on the manuscript. This work is supported by the National Science Foundation (CMMI 1129611 and CBET 1149401), the National Institutes of Health (R21 HL114011 and R21 EB017078), the American Heart Association (12SDG12180025), and the Department of Mechanical Engineering at the University of Michigan, Ann Arbor. The Lurie Nanofabrication Facility at the University of Michigan, a member of the National Nanotechnology Infrastructure Network (NNIN) funded by the National Science Foundation, is acknowledged for support in microfabrication.
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S.W. and J.F. designed experiments; S.W., Y.S. and W.C. performed experiments and modelling; S.W., Y.S. and J.F. analysed data and wrote the manuscript; J.F. supervised the project. All authors edited and approved the final manuscript.
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Weng, S., Shao, Y., Chen, W. et al. Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis. Nature Mater 15, 961–967 (2016). https://doi.org/10.1038/nmat4654
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DOI: https://doi.org/10.1038/nmat4654
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