| First Authors |
Kirstin Meyer
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| Authors |
Kirstin Meyer, Oleksandr Ostrenko, George Bourantas, Hernán Morales-Navarrete, Natalie Porat-Shliom, Fabián Segovia-Miranda, Hidenori Nonaka, Ali Ghaemi, Jean-Marc Verbavatz, Lutz Brusch, Ivo F. Sbalzarini, Yannis Kalaidzidis, Roberto Weigert, Marino Zerial
|
| Corresponding Authors |
Marino Zerial
|
| Last Authors |
Marino Zerial
|
| Journal Name |
Cell systems (Cell Syst) |
| Volume |
4 |
| Issue |
3 |
| Page Range |
277-290 |
| Open Access |
true |
| Print Publication Date |
2017-03-15 |
| Online Publication Date |
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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. |
| PDF |
Meyer_2017_6804.pdf
(5.4 MB)
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| Cover Image |
cover.tif.jpg
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| Affiliated With |
Postdoc first author, Postdocs, Sbalzarini, Zerial
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| Selected By |
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| Acknowledged Services |
EM Facility, Biomedical Services, Light Microscopy Facility
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| Publication Status |
Published |
| Edoc Link |
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| Sfx Link |
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| DOI |
10.1016/j.cels.2017.02.008 |
| PubMed ID |
28330614 |
| WebOfScience Link |
WOS:000399379900006 |
| Alternative Full Text URL |
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| Display Publisher Download Only |
false |
| Visible On MPI-CBG Website |
true |
| PDF Downloadable |
true |
| Created By |
sbalzari |
| Added Date |
2017-03-28 |
| Last Edited By |
herbst |
| Last Edited Date |
2022-01-31 10:18:36.847 |
| Library ID |
6804 |
| Document ID |
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| Entry Complete |
true |
| eDoc Compliant |
true |
| Include in Edoc Report |
true |
| In Pure |
false |
| Ready for eDoc Export |
false |
| Author Affiliations Complete |
false |
| Project Name |
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| Project URL |
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| Grant ID |
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| Funding Programme |
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| Funding Organisation |
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