M9148: HCC
Model 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
2 Lobule radius in 2D slice (lit.): 284.3 µm Hexagon diameter: 284.3 µm * 2 / node.length = 190 0: tangential 1: radial Factor to scale time from 5 min steps to 1 d time/time_span.day Initialization time in days Time in days excluding initialization time (0 ≤ t ≤ time.cell_death). Used for plotting. time.days - time.burn_in Default value for apical adhesive. Value is set per CellType. Common value for all contact energies with hepatocytes involved Common value for //CPM/Interaction/Contact/HomophilicAdhesion/@strength of all possible hepatocyte interactions Time 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 = 3333.3 Global initialization of decay rate. Actual CCl4 depletion occurs only in CellType 'hepatocytes'. cell.type == celltype.medium.id cell.type == celltype.medium.id or cell.type == celltype.CV.id -c.decay*c + (c.target-c)*hepatocyte.lesion.pattern_including_cv node.length*10^-3*(clone.withHSA.outer-clone.withHSA.inner+clone.celldiameter)/2 clone.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)/2 clone.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 inset 1 1 Cell 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.division time.days rand_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.division time.days rand_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)) 2 3 plot at least every 144 time steps = 0.5d to select plots for 1008=3d, 1584=5d, 2016=6.5d as in Fig.3