Notch in mechanotransduction–from molecular mechanosensitivityto tissue mechanostasis

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36 Citaten (Scopus)

Samenvatting

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.
Originele taal-2Engels
Artikelnummerjcs250738
Aantal pagina's14
TijdschriftJournal of Cell Science
Volume133
Nummer van het tijdschrift24
DOI's
StatusGepubliceerd - 21 dec. 2020

Financiering

FinanciersFinanciernummer
NOW
Horizon 2020 Framework Programme771168
European Research Council
Suomen Akatemia33041, 218062
Nederlandse Organisatie voor Wetenschappelijk Onderzoek019.183EN.025
Meningitis Now

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