M9148: HCCModel ID: https://identifiers.org/morpheus/M9148
Title: Hepatocellular Carcinoma
Authors: S. Höhme, F. Bertaux, W. Weens, B. Grasl-Kraupp, J. G. Hengstler, D. Drasdo
Submitters: L. Brusch, D. Jahn
Curators: L. Brusch, D. Jahn
Date: 12.04.2024
Software: Morpheus (open source). Download from: https://morpheus.gitlab.io
Units: [time] = 1 d
[space] = 3 µm
Reference: This model reproduces a published result, originally obtained with a different simulator:
S. Höhme, F. Bertaux, W. Weens, B. Grasl-Kraupp, J. G. Hengstler, D. Drasdo: Model Prediction and Validation of an Order Mechanism Controlling the Spatiotemporal Phenotype of Early Hepatocellular Carcinoma. Bull. Math. Biol. 80, 1134–1171, 2018.
https://doi.org/10.1007/s11538-017-0375-1
2Lobule radius in 2D slice (lit.): 284.3 µm
Hexagon diameter: 284.3 µm * 2 / node.length = 1900: tangential
1: radialFactor to scale time from 5 min steps to 1 dtime/time_span.dayInitialization time in daysTime in days excluding initialization time (0 ≤ t ≤ time.cell_death). Used for plotting.time.days - time.burn_inDefault value for apical adhesive. Value is set per CellType.Common value for all contact energies with hepatocytes involvedCommon value for //CPM/Interaction/Contact/HomophilicAdhesion/@strength of all possible hepatocyte interactionsTime of one cell cycle in days (Table 2 in Hoehme et al. 2018)Diffusion constant converted from cm^2/s to 3 µm^2/5 min:
10e-6 cm^2/s = 10e-6 * (10^4)^2 µm^2/s = 10e-6 * (10^4)^2 / 3^2 (3 µm)^2/s = 10^-6 * 10^8 / 9 * 300 (3 µm)^2/5 min = 3333.3Global initialization of decay rate. Actual CCl4 depletion occurs only in CellType 'hepatocytes'.cell.type == celltype.medium.idcell.type == celltype.medium.id or cell.type == celltype.CV.id-c.decay*c + (c.target-c)*hepatocyte.lesion.pattern_including_cvnode.length*10^-3*(clone.withHSA.outer-clone.withHSA.inner+clone.celldiameter)/2clone.withHSA.area/(pi*clone.withHSA.radialspan)max(clone.withHSA.radialspan,clone.withHSA.tangentialspan)/min(clone.withHSA.radialspan,clone.withHSA.tangentialspan)node.length*10^-3*(clone.withoutHSA.outer-clone.withoutHSA.inner+clone.celldiameter)/2clone.withoutHSA.area/(pi*clone.withoutHSA.radialspan)max(clone.withoutHSA.radialspan,clone.withoutHSA.tangentialspan)/min(clone.withoutHSA.radialspan,clone.withoutHSA.tangentialspan)Delta tau [d] = 2h from Ad(A-5) in Hoehme et al. 2018, but *2 to match Fig.14 inset11Cell diameter (lit.): 23.3 µm
CCl4 depletion occurs only in hepatocytes, i.e. CCl4 decay rate is 0 at in all other locations.Assign the value "1" to the MembraneProperty on apical sides (± 45°; ± π/4) of the hepatocytes. Needed for homophilic adhesion.
- Use cos() version for apical sides perpendicular to sinusoids (tangential).
- Use sin() version for apical sides parallel to sinusoids (radial).apical.polarization == 0 ? (abs(cos(membrane.phi - hepatocyte.sinusoid_mean.phi)) <= sin(pi/4) ? 1 : 0) : (abs(sin(membrane.phi - hepatocyte.sinusoid_mean.phi)) <= sin(pi/4) ? 1 : 0)Cell diameter (lit.): 23.3 µm
Assign the value "1" to the MembraneProperty on apical sides (± 45°; ± π/4) of the hepatocytes. Needed for homophilic adhesion.
- Use cos() version for apical sides perpendicular to sinusoids (tangential).
- Use sin() version for apical sides parallel to sinusoids (radial).apical.polarization == 0 ? (abs(cos(membrane.phi - hepatocyte.sinusoid_mean.phi)) <= sin(pi/4) ? 1 : 0) : (abs(sin(membrane.phi - hepatocyte.sinusoid_mean.phi)) <= sin(pi/4) ? 1 : 0)time.days >= hepatocyte.time.birth+hepatocyte.time.divisiontime.daysrand_norm(hepatocyte.time_span.cell_cycle,hepatocyte.time_span.cell_cycle_delta)if(hepatocyte.time.nextdivision < (hepatocyte.time_span.cell_cycle - hepatocyte.time_span.cell_cycle_delta), (hepatocyte.time_span.cell_cycle - hepatocyte.time_span.cell_cycle_delta),
if(hepatocyte.time.nextdivision > (hepatocyte.time_span.cell_cycle + hepatocyte.time_span.cell_cycle_delta), (hepatocyte.time_span.cell_cycle + hepatocyte.time_span.cell_cycle_delta), hepatocyte.time.nextdivision))Cell diameter (lit.): 23.3 µm
Assign the value "1" to the MembraneProperty on apical sides (± 45°; ± π/4) of the hepatocytes. Needed for homophilic adhesion.
- Use cos() version for apical sides perpendicular to sinusoids (tangential).
- Use sin() version for apical sides parallel to sinusoids (radial).apical.polarization == 0 ? (abs(cos(membrane.phi - hepatocyte.sinusoid_mean.phi)) <= sin(pi/4) ? 1 : 0) : (abs(sin(membrane.phi - hepatocyte.sinusoid_mean.phi)) <= sin(pi/4) ? 1 : 0)time.days >= hepatocyte.time.birth+hepatocyte.time.divisiontime.daysrand_norm(hepatocyte.time_span.cell_cycle,hepatocyte.time_span.cell_cycle_delta)if(hepatocyte.time.nextdivision < (hepatocyte.time_span.cell_cycle - hepatocyte.time_span.cell_cycle_delta), (hepatocyte.time_span.cell_cycle - hepatocyte.time_span.cell_cycle_delta),
if(hepatocyte.time.nextdivision > (hepatocyte.time_span.cell_cycle + hepatocyte.time_span.cell_cycle_delta), (hepatocyte.time_span.cell_cycle + hepatocyte.time_span.cell_cycle_delta), hepatocyte.time.nextdivision))23plot at least every 144 time steps = 0.5d to select plots for 1008=3d, 1584=5d, 2016=6.5d as in Fig.3-0.326*ln(celltype.HCC_with_HSA.size)+3.55-0.195*ln(celltype.HCC_with_HSA.size)+2.44-0.130*ln(celltype.HCC_without_HSA.size)+2.28-0.029*ln(celltype.HCC_without_HSA.size)+1.24Hepatocyte density (lit.): 1889 cells/mm^2
Lobule area in 2D slice (lit.): 0.21 mm^2
- Hepatocyte lesion without hepatocytes, i.e. with medium only (model): 0.2043646748 mm^2 → 386 cells
- Lobule area, i.e. includung medium, hepatocytes, CV, PVs (model): 0.2132578897 mm^2 → 403 cellsCentral vein radius (lit.): 41.2 µm