A Predictive 3D Multi-Scale Model of Biliary Fluid Dynamics in the Liver Lobule

Cell Syst. 2017 Mar 22;4(3):277-290.e9. doi: 10.1016/j.cels.2017.02.008. Epub 2017 Mar 18.


Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed a predictive 3D multi-scale model that simulates fluid dynamic properties successively from the subcellular to the tissue level. The model integrates the structure of the bile canalicular network in the mouse liver lobule, as determined by high-resolution confocal and serial block-face scanning electron microscopy, with measurements of bile transport by intravital microscopy. The combined experiment-theory approach revealed spatial heterogeneities of biliary geometry and hepatocyte transport activity. Based on this, our model predicts gradients of bile velocity and pressure in the liver lobule. Validation of the model predictions by pharmacological inhibition of Rho kinase demonstrated a requirement of canaliculi contractility for bile flow in vivo. Our model can be applied to functionally characterize liver diseases and quantitatively estimate biliary transport upon drug-induced liver injury.

Keywords: acetaminophen; actomyosin contractility; bile canaliculi; bile flow; cholestasis; computational fluid dynamics; drug-induced liver injury; mouse liver; multi-scale model; peristalsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile / metabolism
  • Bile Canaliculi / metabolism*
  • Bile Canaliculi / physiology*
  • Biliary Tract / diagnostic imaging*
  • Biliary Tract / metabolism
  • Biliary Tract / physiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Cholestasis / metabolism
  • Computer Simulation
  • Forecasting
  • Hepatocytes / metabolism
  • Hydrodynamics
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL