Liquid-crystal organization of liver tissue

Elife. 2019 Jun 17;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.

Keywords: 3D tissue organization; cell polarity; liquid crystal order; liver; mouse; physics of living systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Capillaries / chemistry
  • Capillaries / cytology
  • Capillaries / metabolism
  • Cell Polarity*
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Female
  • Hepatocytes / chemistry
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Liquid Crystals / chemistry*
  • Liver / blood supply
  • Liver / chemistry
  • Liver / cytology*
  • Male
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • RNA Interference

Substances

  • Integrin beta1