Matrix viscoelasticity controls spatiotemporal tissue organization

Elosegui-Artola, Alberto and Gupta, Anupam and Najibi, Alexander J. and et al, . (2022) Matrix viscoelasticity controls spatiotemporal tissue organization. Nature Materials. ISSN 1476-1122

Full text not available from this repository. (Request a copy)

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. © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

[error in script]

IITH Creators:

IITH Creators	ORCiD
Gupta, Anupam	https://orcid.org/0000-0002-7335-0584

Item Type:

Article

Additional Information:

We thank M. Sobral, M. Dellacherie, J. Lou, M. Uroz and all the members of the Mooney lab for helpful discussions and comments on the manuscript. This work was supported by funding from the Wellcome Leap HOPE Program (D.J.M). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 851055) (A.E.-A.). A.E.-A. received funding for this work from the European Union’s Horizon 2020 research and innovation programme through a Marie Sklodowska-Curie grant agreement number 798504 (MECHANOSITY). A.J.N. acknowledges a Graduate Research Fellowship from the National Science Foundation. This work was partly supported by funding (R01 DK125817 and Tri-SCI grant) to QZ. I.d.L. was supported by the National Cancer Institute of the National Institutes of Health under award number U01CA214369. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Uncontrolled Keywords:

Cell proliferation; Stress relaxation; Tissue

Subjects:

Physics
Physics > Modern physics

Divisions:

Department of Physics

Depositing User:

Ms Palak Jain

Date Deposited:

22 May 2023 09:24

Last Modified:

22 May 2023 09:24