Letter | Published:

Extracellular matrix scaffolding guides lumen elongation by inducing anisotropic intercellular mechanical tension

Nature Cell Biology volume 18, pages 311318 (2016) | Download Citation

Abstract

The de novo formation of secretory lumens plays an important role during organogenesis. It involves the establishment of a cellular apical pole1 and the elongation of luminal cavities2. The molecular parameters controlling cell polarization have been heavily scrutinized3,4,5. In particular, signalling from the extracellular matrix (ECM) proved essential to the proper localization of the apical pole by directed protein transport6. However, little is known about the regulation of the shape and the directional development of lumen into tubes. We demonstrate that the spatial scaffolding of cells by ECM can control tube shapes and can direct their elongation. We developed a minimal organ approach comprising of hepatocyte doublets cultured in artificial microniches to precisely control the spatial organization of cellular adhesions in three dimensions. This approach revealed a mechanism by which the spatial repartition of integrin-based adhesion can elicit an anisotropic intercellular mechanical stress guiding the osmotically driven elongation of lumens in the direction of minimal tension. This mechanical guidance accounts for the different morphologies of lumen in various microenvironmental conditions.

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Acknowledgements

The authors thank S. Wolf, A. Wong and L. Bulavina for their help with manuscript writing and illustration. We thank J. J. Fan and S. Mo for in vivo imaging. We thank T. Saunders and R. Zaidel-Bar for insightful comments on the manuscripts. This work was supported mostly by MBI and IBN core funding, NRF grant CRP 001-084, and ANR grant Defis generique 2014.

Author information

Author notes

    • Qiushi Li
    •  & Yue Zhang

    These authors contributed equally to this work.

    • Hanry Yu
    •  & Virgile Viasnoff

    These authors jointly supervised this work.

Affiliations

  1. Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore

    • Qiushi Li
    • , Yue Zhang
    • , Jeffrey Robens
    • , Hanry Yu
    •  & Virgile Viasnoff
  2. Department of Biological Sciences, National University of Singapore, Singapore 117411, Singapore

    • Perrine Pluchon
    •  & Virgile Viasnoff
  3. Institute of Molecular Cell Biology, ASTAR, 61 Biopolis Drive, Singapore 138673, Singapore

    • Keira Herr
    • , Jean-Paul Thiery
    •  & Virgile Viasnoff
  4. Laboratoire d’Ingénierie des Systèmes Biologiques et des Procédés, Université de Toulouse, INSA, INRA, CNRS, 31077 Toulouse, France

    • Myriam Mercade
  5. Department of Physiology, Yong Loo Lin School of Medicine, National University Health System, Singapore 117597, Singapore

    • Hanry Yu
  6. Institute of Bioengineering and Nanotechnology (IBN), Agency for Science, Technology and Research, Singapore 138669, Singapore

    • Hanry Yu
  7. CNRS UMI3639, Singapore 117411, Singapore

    • Virgile Viasnoff

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Contributions

Q.L. and Y.Z. performed most of the experiments. Q.L., Y.Z. and V.V. designed the experiments. H.Y. and V.V. initiated the work. J.R., P.P., M.M., K.H., J.-P.T. and H.Y. contributed substantially in helping the realization of the experiments. V.V. and H.Y. jointly supervised the work of Q.L. Q.L., Y.Z. and V.V. wrote the article.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Virgile Viasnoff.

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Videos

  1. 1.

    Time lapse imaging (1 image every 2 minutes) of canaliculi growth in collagen 1 sandwich culture.

    The film starts right after the overlay of the hepatocytes with the collagen gel and it lasts for 5 hours. Notice that the elongation of the canaliculi involves the separation of contacting membranes at the cell/cell contact. The canaliculi extend more along the contact in the direction of neighboring cells than orthogonally to the contact or vertically.

  2. 2.

    Schematic representation of hepatocyte doublets in circular microwells in the F/F coating configuration.

  3. 3.

    Schematic representation of hepatocyte doublets in circular microwells in the P/F coating configuration.

  4. 4.

    Schematic representation of hepatocyte doublets in circular microwells in the F/P coating configuration.

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DOI

https://doi.org/10.1038/ncb3310

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