A2 Refereed review article in a scientific journal
Notch in mechanotransduction - from molecular mechanosensitivity to tissue mechanostasis
Authors: Stassen Oscar MJA, Ristori Tommaso, Sahlgren Cecilia M
Publisher: Company of Biologists Ltd
Publication year: 2020
Journal: Journal of Cell Science
Journal name in source: Journal of cell science
Journal acronym: J Cell Sci
Article number: jcs250738
Volume: 133
Issue: 24
Number of pages: 14
ISSN: 0021-9533
eISSN: 1477-9137
DOI: https://doi.org/10.1242/jcs.250738
Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/52215637
Tissue development and homeostasis are controlled by mechanical cues. Perturbation of the mechanical equilibrium triggers restoration of mechanostasis through changes in cell behavior, while defects in these restorative mechanisms lead to mechanopathologies, for example, osteoporosis, myopathies, fibrosis or cardiovascular disease. Therefore, sensing mechanical cues and integrating them with the biomolecular cell fate machinery is essential for the maintenance of health. The Notch signaling pathway regulates cell and tissue fate in nearly all tissues. Notch activation is directly and indirectly mechanosensitive, and regulation of Notch signaling, and consequently cell fate, is integral to the cellular response to mechanical cues. Fully understanding the dynamic relationship between molecular signaling, tissue mechanics and tissue remodeling is challenging. To address this challenge, engineered microtissues and computational models play an increasingly large role. In this Review, we propose that Notch takes on the role of a 'mechanostat', maintaining the mechanical equilibrium of tissues. We discuss the reciprocal role of Notch in the regulation of tissue mechanics, with an emphasis on cardiovascular tissues, and the potential of computational and engineering approaches to unravel the complex dynamic relationship between mechanics and signaling in the maintenance of cell and tissue mechanostasis.
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