Liquid-crystal organization of liver tissue
- Max Planck Institute of Molecular Cell Biology and Genetics, Germany
- Max Planck Institute for the Physics of Complex Systems, Germany
- Technische Universität Dresden, Germany
- Massachusetts Institute of Technology, United States
- Skolkovo Institute of Science and Technology, Russia
- MV Lomonosov Moscow State University, Russia
- TU Dresden, Germany
Figures
Figure 1 with 6 supplements
Multi-resolution imaging and 3D reconstruction of the mouse liver lobule.
(A, B) Low-resolution imaging of an optically cleared liver tissue slice, stained for hepatocyte cell borders (cyan, Phalloidin) and nuclei (gray, DAPI); voxel size 1 μm x 1 μm x 1 μm. Central veins …
Figure 1—figure supplement 1
Colocalization of sinusoids and basal plasma membrane.
High-resolution images of samples for control conditions (top, siRNA against Luciferase) and Integrin-β1 knock down (bottom, siRNA against Integrin-β1 receptor) are shown. Samples were stained for …
Figure 1—figure supplement 2
Quantitative structural parameters of hepatocytes along CV-PV axis.
Structural parameters of hepatocytes for wild type (black), Luciferase control (blue), Integrin-β1 knockdown (red). As described in Meyer et al. (2017); Morales-Navarrete et al., 2015 the CV-PV axis …
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Figure 1—figure supplement 2—source data 1
Raw data structural parameters of hepatocytes along CV-PV axis.
- https://doi.org/10.7554/eLife.44860.005
Figure 1—figure supplement 3
Quantitative structural parameters of sinusoidal and BC networks along CV-PV axis.
Structural parameters of the sinusoidal and BC networks for wild type (black), Luciferase control (blue), Integrin-β1 knockdown (red). The CV-PV axis was divided in 10 zones (from 0 to 10), showing …
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Figure 1—figure supplement 3—source data 1
Raw data structural parameters of sinusoidal and BC networks along CV-PV axis.
- https://doi.org/10.7554/eLife.44860.007
Figure 1—video 1
Supplementary video for Figure 1C. Tissue-level reconstruction of the liver lobule.
Digital reconstruction of large veins in mouse liver tissue, generated from low-resolution 3D images of serial slices (CV: cyan, PV: orange. Dimensions of imaging box: approximately 1 mm x 1 mm x 1mm.
Figure 1—video 2
Supplementary video for Figure 1E.
Cellular-level reconstruction of liver tissue. 3D high-resolution reconstruction of main components of liver tissue: CV (cyan), PV (orange), sinusoidal network (magenta), bile canaliculi network …
Figure 1—video 3
Supplementary video for Figure 1F.
Subcellular-level reconstruction of liver tissue. Single hepatocyte showing apical (green), basal (magenta) and lateral (gray) plasma membrane domains, reconstructed from high-resolution 3D images.
Figure 2 with 2 supplements
Biaxial cell polarity of hepatocytes.
(A) Idealized representation of simple cell polarity, as found in cells of sheet-like epithelial tissue, showing schematic representation, spherical projection and Mollweide cartographic projection (…
Figure 2—figure supplement 1
Biaxial cell polarity of basal plasma membrane distribution.
(A, C, E) Respective weights of bipolar axis () and ring axis () for reconstructed hepatocytes, defined in terms of the eigenvalues of the nematic cell polarity tensor for the apical …
Figure 2—figure supplement 2
Hepatocyte shape anisotropy.
Cell shape axis were defined in terms of a second-moments tensor with components , where the integral extends over the whole (non-projected) surface of each hepatocyte. The eigenvalues and …
Figure 3 with 2 supplements
Lobule-level organization of nematic cell polarity.
(A) Bipolar cell polarity axes of apical plasma membrane distribution () shown as lines of constant length for individual hepatocytes at their respective position in the lobule. (B) Same as A …
Figure 3—figure supplement 1
Anisotropy of BC network.
Quantification of alignment with local reference direction for the preferred direction of the local BC network surrounding each hepatocyte (), analogous to Figure 3G. Statistics: n=3 independent …
Figure 3—figure supplement 2
Control for layered order in the liver lobule.
(A) Region-of-interest (ROI) in the central region of a liver lobule, with CV (cyan) and PV (orange) serving as landmarks; identical to inset of Figure 3H. Inside the ROI, the density of sinusoids …
Figure 4 with 2 supplements
Liquid-crystal order, but not biaxial polarity of hepatocytes, is perturbed in Integrin-β1 KD mice.
(A) Silencing Integrin-β1 in the liver results in distortion of both bile canalicular and sinusoidal networks, with reduced apparent alignment with the CV-PV axis in comparison to control …
Figure 4—figure supplement 1
Analysis of the Integrin-β1 expression by immunofluorescence staining.
A) High-resolution images of liver samples for control conditions (top, siRNA against Luciferase) and Integrin-β1 knock down (bottom, siRNA against Integrin-β1) showing staining for the sinusoidal …
Figure 4—figure supplement 2
Disturbed nematic liquid-crystal order in Integrin-β1 knock-down.
(A) Bipolar cell polarity axes of apical plasma membrane distribution () shown as lines of constant length for individual hepatocytes at their respective position in the lobule after local …
Figure 5
Proposed model of liver tissue architecture.
(A) Our work proposes a new multi-scale model of liver architecture, characterized by liquid-crystal order of hepatocytes with biaxial nematic cell polarity, co-alignment of hepatocyte polarity and …
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Antibody | anti-Flk-1 (goat polyclonal) | R and D system | AF644 / RRID:AB_355500 | (1:200) |
| Antibody | anti-laminin (rabbit polyclonal) | Sigma | L9393/RRID:AB_477163 | (1:5000) |
| Antibody | anti-fibronectin (rabbit polyclonal) | Millipore | AB2033/RRID:AB_2105702 | (1:1000) |
| Antibody | anti-CD13 (rat monoclonal) | Novus | NB100−64843/RRID:AB_959651 | (1:500) |
| Antibody | anti-integrin ß1 (rat monoclonal) | Millipore | MAB1997/RRID:AB_2128202 | (1:1000) |
| Antibody | Donkey anti-goat Alexa Fluor 647 | Invitrogen | A21447/RRID:AB_2535864 | (1:1000) |
| Antibody | Donkey anti-rabbit Alexa Fluor 647 | Invitrogen | A31573/RRID:AB_2536183 | (1:1000) |
| Antibody | Donkey anti-rat CF 568 | Biotium | 20092/RRID:AB_10559037 | (1:1000) |
| Other | Phalloidin-488 | LIFE technologies | A12379/RRID:AB_2315147 | (1:150) |
| Other | Dapi | LIFE technologies | D1306/RRID:AB_2629482 | (1 µg/ml) |
| Sequence-based reagent | LNP-formulated siRNAs against luciferase | Bogorad et al., 2014 | (1 mgKg-1) | |
| Sequence-based reagent | LNP-formulated siRNAs against Integrin-ß1 | Bogorad et al., 2014 | (1 mgKg-1) | |
| Strain, strain background (M. musculus C57BL/6JOlaHsd) | Wild type, Luciferase, Integrin-ß1 knock down | Charles River Laboratory | ||
| Software, algorithm | MotionTracking | Morales-Navarrete et al., 2015 | ||
| Software, algorithm | MuSiCal | Agarwal and Macháň, 2016 |
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.44860.021
