Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Centre for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany
Kirstin Meyer
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Roman L Bogorad
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States
Victor Koteliansky
Skolkovo Institute of Science and Technology, Skolkovo, Russia; Department of Chemistry, MV Lomonosov Moscow State University, Moscow, Russia
Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany; Center for Advancing Electronics Dresden, Technische Universität Dresden, Dresden, Germany
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.
