title: Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis.
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). 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.
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Shinuo
authors.initials: S
authors.lastname: Weng
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.|Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
mesh_terms: D001696:Biomechanical Phenomena; D022001:Focal Adhesions; D006706:Homeostasis; D042541:Intracellular Space / Q000378:metabolism*; D055595:Mechanical Phenomena; D008954:Models, Biological; D059010:Single-Cell Analysis