1. Physics of Living Systems
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Liquid-crystal organization of liver tissue

  1. Hernán Morales-Navarrete
  2. Hidenori Nonaka
  3. Andre Scholich
  4. Fabián Segovia-Miranda
  5. Walter de Back
  6. Kirstin Meyer
  7. Roman L Bogorad
  8. Victor Koteliansky
  9. Lutz Brusch
  10. Yannis Kalaidzidis  Is a corresponding author
  11. Frank Jülicher  Is a corresponding author
  12. Benjamin M Friedrich  Is a corresponding author
  13. Marino Zerial  Is a corresponding author
  1. Max Planck Institute for Cell Biology and Genetics, Germany
  2. Max Planck Institute for the Physics of Complex Systems, Germany
  3. Technische Universität Dresden, Germany
  4. Massachusetts Institute of Technology, United States
  5. Skolkovo Institute of Science and Technology, Russian Federation
Research Article
  • Cited 11
  • Views 3,222
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Cite this article as: eLife 2019;8:e44860 doi: 10.7554/eLife.44860

Abstract

Functional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images of mouse liver tissue and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells, since silencing Integrin-β1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1-figure supplement 2 and Figure 1-figure supplement 3

Article and author information

Author details

  1. Hernán Morales-Navarrete

    Max Planck Institute for Cell Biology and Genetics, Dresden, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9578-2556
  2. Hidenori Nonaka

    Max Planck Institute for Cell Biology and Genetics, Dresden, Germany
    Competing interests
    No competing interests declared.
  3. Andre Scholich

    Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9393-5459
  4. Fabián Segovia-Miranda

    Max Planck Institute for Cell Biology and Genetics, Dresden, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1546-0475
  5. Walter de Back

    Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4641-8472
  6. Kirstin Meyer

    Max Planck Institute for Cell Biology and Genetics, Dresden, Germany
    Competing interests
    No competing interests declared.
  7. Roman L Bogorad

    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
  8. Victor Koteliansky

    Skolkovo Institute of Science and Technology, Skolkovo, Russian Federation
    Competing interests
    No competing interests declared.
  9. Lutz Brusch

    Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0137-5106
  10. Yannis Kalaidzidis

    Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    For correspondence
    kalaidzi@mpi-cbg.de
    Competing interests
    No competing interests declared.
  11. Frank Jülicher

    Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
    For correspondence
    julicher@pks.mpg.de
    Competing interests
    Frank Jülicher, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4731-9185
  12. Benjamin M Friedrich

    Center for Advancing Electronics, Technische Universität Dresden, Dresden, Germany
    For correspondence
    benjamin.m.friedrich@tu-dresden.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9742-6555
  13. Marino Zerial

    Max Planck Institute for Cell Biology and Genetics, Dresden, Germany
    For correspondence
    zerial@mpi-cbg.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7490-4235

Funding

H2020 European Research Council (Grant number 695646)

  • Hernán Morales-Navarrete

Bundesministerium für Bildung und Forschung (LiSyM-031L0038)

  • Fabián Segovia-Miranda
  • Kirstin Meyer

Deutsche Forschungsgemeinschaft (Cluster of Excellence EXC 1056 cfaed)

  • Benjamin M Friedrich

Max-Planck-Gesellschaft (Open-access funding)

  • Hidenori Nonaka

Bundesministerium für Bildung und Forschung (SYSBIO II-031L0044)

  • Fabián Segovia-Miranda
  • Kirstin Meyer

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were performed in compliance with German animal welfarelegislation and in pathogen-free conditions in the animal facility ofthe MPI-CBG, Dresden, Germany. Protocols were approved by theInstitutional Animal Welfare Officer (Tierschutzbeauftragter) and allnecessary licenses were obtained from the regional Ethical Commissionfor Animal Experimentation of Dresden, Germany (Tierversuchskommission,Landesdirektion Dresden)(License number: DD24-5131/338/50).

Reviewing Editor

  1. Pierre Sens, Institut Curie, PSL Research University, CNRS, France

Publication history

  1. Received: January 4, 2019
  2. Accepted: June 14, 2019
  3. Accepted Manuscript published: June 17, 2019 (version 1)
  4. Version of Record published: June 28, 2019 (version 2)

Copyright

© 2019, Morales-Navarrete et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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