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Matrix viscoelasticity controls spatiotemporal tissue organization.

Alberto Elosegui-Artola1,2,3,4,5, Anupam Gupta1,6, Alexander J Najibi1,2

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The extracellular matrix

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Area of Science:

  • Biomaterials Science
  • Developmental Biology
  • Cell Biology

Background:

  • The extracellular matrix (ECM) provides physical and biochemical cues that regulate cell behavior.
  • The role of ECM viscoelasticity in collective cell organization and tissue patterning remains unclear.

Purpose of the Study:

  • To investigate how matrix viscoelasticity influences the spatial and temporal organization of collective cell dynamics.
  • To elucidate the mechanisms by which ECM properties guide tissue proliferation and morphogenesis.

Main Methods:

  • In vitro and in vivo experiments using breast epithelial cell spheroids.
  • Computational modeling to establish a phase diagram of tissue morphology.
  • Biochemical assays and intestinal organoid experiments for validation.

Main Results:

  • Matrix viscoelasticity induces symmetry breaking in spheroids, leading to finger-like protrusions.
  • Observed YAP nuclear translocation and epithelial-to-mesenchymal transition (EMT) in an Arp2/3-complex-dependent manner.
  • Developed a phase diagram predicting tissue morphology based on viscoelastic properties and cellular parameters.

Conclusions:

  • Passive matrix viscoelasticity is a key regulator of tissue growth dynamics.
  • Stress relaxation mechanisms within the ECM are crucial for morphogenesis and oncogenesis.
  • Findings provide insights into tissue patterning and disease development.