Skip to Main content Skip to Navigation
Journal articles

Intravital dynamic and correlative imaging reveals diffusion‐dominated canalicular and flow‐augmented ductular bile flux

Abstract : Small-molecule flux in tissue-microdomains is essential for organ function, but knowledge of this process is scant due to the lack of suitable methods. We developed two independent techniques that allow the quantification of advection (flow) and diffusion in individual bile canaliculi and in interlobular bile ducts of intact livers in living mice, namely Fluorescence Loss After Photoactivation (FLAP) and Intravital Arbitrary Region Image Correlation Spectroscopy (IVARICS). The results challenge the prevailing 'mechano-osmotic' theory of canalicular bile flow. After active transport across hepatocyte membranes bile acids are transported in the canaliculi primarily by diffusion. Only in the interlobular ducts, diffusion is augmented by regulatable advection. Photoactivation of fluorescein bis-(5-carboxymethoxy-2-nitrobenzyl)-ether (CMNB-caged fluorescein) in entire lobules demonstrated the establishment of diffusive gradients in the bile canalicular network and the sink function of interlobular ducts. In contrast to the bile canalicular network, vectorial transport was detected and quantified in the mesh of interlobular bile ducts. In conclusion, the liver consists of a diffusion dominated canalicular domain, where hepatocytes secrete small molecules and generate a concentration gradient and a flow-augmented ductular domain, where regulated water influx creates unidirectional advection that augments the diffusive flux.
Complete list of metadata

https://hal.inria.fr/hal-03135253
Contributor : Irene Vignon-Clementel Connect in order to contact the contributor
Submitted on : Monday, February 8, 2021 - 7:39:20 PM
Last modification on : Wednesday, January 26, 2022 - 3:34:13 AM
Long-term archiving on: : Sunday, May 9, 2021 - 8:48:08 PM

File

hep.31422.pdf
Files produced by the author(s)

Identifiers

Citation

Nachiket Vartak, Georgia Guenther, Florian Joly, Amruta Damle-Vartak, Gudrun Wibbelt, et al.. Intravital dynamic and correlative imaging reveals diffusion‐dominated canalicular and flow‐augmented ductular bile flux. Hepatology, Wiley-Blackwell, 2021, 73 (4), pp.1531-1550. ⟨10.1002/hep.31422⟩. ⟨hal-03135253⟩

Share

Metrics

Les métriques sont temporairement indisponibles