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Cited by 91Liver physiology and pathologyDrug Transport and Resistance MechanismsOrgan Transplantation Techniques and Outcomes

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

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Meyer, Kirstin, Ostrenko, Oleksandr, Bourantas, Georgios, Morales-Navarrete, Hernan, Porat-Shliom, Natalie, Segovia-Miranda, Fabian, Nonaka, Hidenori, Ghaemi, Ali +6 more·2017·Cell Systems
DOI 10.1016/j.cels.2017.02.008PMC PMC8063490
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Abstract

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.

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Authors
Meyer, K., Ostrenko, O., Bourantas, G., Morales-Navarrete, H., Porat-Shliom, N., Segovia-Miranda, F., Nonaka, H., Ghaemi, A., Verbavatz, J.-M., Brusch, L., Sbalzarini, I., Kalaidzidis, Y., Weigert, R., & Zerial, M.
Affiliations
  • Max Planck Institute of Molecular Cell Biology and Genetics (DE)
  • Center for Advancing Electronics Dresden (DE)
  • Lomonosov Moscow State University (RU)
  • National Institutes of Health (US)
Corresponding author
Zerial, Marino
ORCID
Venue
Cell Systems
Publisher
Elsevier BV
Published
2017-03
Volume
4
Issue
3
Pages
277-290.e9
ISSN
2405-4712 (ISSN-L)
DOI
10.1016/j.cels.2017.02.008
PMC
PMC8063490
OpenAlex
W2596378254
Cited by
91
References
63
Citations by year
2026: 6 · 2025: 2 · 2024: 6 · 2023: 15 · 2022: 6 · 2021: 16 · 2020: 19 · 2019: 12 · 2018: 5 · 2017: 4
FWCI
6.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Systems (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • Virtual Liver (315757)
  • Liver Systems Medicine (031L0038)
  • German Federal Ministry of Research and Education (031L0044)
  • European Research Council (695646)
  • Max Planck Society
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
Keywords
bile flow, bile canaliculi, liver lobule, cholestasis, Rho kinase, drug-induced liver injury, mouse liver
MeSH terms
Animals, Bile, Bile Canaliculi, Biliary Tract, Cholestasis, Computer Simulation, Forecasting, Liver, Mice, Inbred C57BL, Hepatocytes, Mice, Chemical and Drug Induced Liver Injury, Hydrodynamics

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