Hartman Institute for Therapeutic Organ Regeneration

Matrix viscoelasticity controls spatiotemporal tissue organization.

TitleMatrix viscoelasticity controls spatiotemporal tissue organization.
Publication TypeJournal Article
Year of Publication2023
AuthorsElosegui-Artola A, Gupta A, Najibi AJ, Seo BRi, Garry R, Tringides CM, de Lázaro I, Darnell M, Gu W, Zhou Q, Weitz DA, Mahadevan L, Mooney DJ
JournalNat Mater
Volume22
Issue1
Pagination117-127
Date Published2023 Jan
ISSN1476-4660
KeywordsElasticity, Epithelial Cells, Extracellular Matrix, Viscosity
Abstract

<p>Biomolecular and physical cues of the extracellular matrix environment regulate collective cell dynamics and tissue patterning. Nonetheless, how the viscoelastic properties of the matrix regulate collective cell spatial and temporal organization is not fully understood. Here we show that the passive viscoelastic properties of the matrix encapsulating a spheroidal tissue of breast epithelial cells guide tissue proliferation in space and in time. Matrix viscoelasticity prompts symmetry breaking of the spheroid, leading to the formation of invading finger-like protrusions, YAP nuclear translocation and epithelial-to-mesenchymal transition both in vitro and in vivo in a Arp2/3-complex-dependent manner. Computational modelling of these observations allows us to establish a phase diagram relating morphological stability with matrix viscoelasticity, tissue viscosity, cell motility and cell division rate, which is experimentally validated by biochemical assays and in vitro experiments with an intestinal organoid. Altogether, this work highlights the role of stress relaxation mechanisms in tissue growth dynamics, a fundamental process in morphogenesis and oncogenesis.</p>

DOI10.1038/s41563-022-01400-4
Alternate JournalNat Mater
PubMed ID36456871
PubMed Central IDPMC10332325
Grant List / WT_ / Wellcome Trust / United Kingdom
R01 DK125817 / DK / NIDDK NIH HHS / United States
U01 CA214369 / CA / NCI NIH HHS / United States

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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