Matrix viscoelasticity controls spatiotemporal tissue organization

Alberto Elosegui-Artola, Anupam Gupta, Alexander J. Najibi, Bo Ri Seo, Ryan Garry, Christina M. Tringides, Irene de Lázaro, Max Darnell, Wei Gu, Qiao Zhou, David A. Weitz, L. Mahadevan, David J. Mooney

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalNature Materials
Volume22
Issue number1
DOIs
StatePublished - Jan 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

Fingerprint

Dive into the research topics of 'Matrix viscoelasticity controls spatiotemporal tissue organization'. Together they form a unique fingerprint.

Cite this