Mitosis_O2 — Cell spheroid oxygen-driven growth model

This repository contains a CompuCell3D simulation modeling oxygen-driven growth, fate and mitosis of a single-cell-initiated spheroid. The model demonstrates a two-threshold oxygen-driven phenotype switching (Normoxic → Hypoxic → Necrotic), deterministic growth of normoxic cells, and optional radiotherapy using a linear-quadratic (LQ) kill model.

Key components

• mitosis_O2.cc3d — CompuCell3D project file (entry point for the GUI runner).
• Simulation/mitosis_O2.py — Main Python runner that registers steppables and starts the simulation.
• Simulation/mitosis_O2.xml — CompuCell3D XML configuration containing the Potts model settings and UserParameters used by steppables.
• Simulation/mitosis_O2Steppables.py — Python steppables implementing initialization, oxygen-driven fate and growth, mitosis, radiotherapy, compaction, and light analysis/plotting.

Model overview

• Geometry: 3D Potts model with domain size defined in mitosis_O2.xml (default 100x100x100 voxels).

• Cell types:

  • Medium (TypeId=0)
  • Normoxic (TypeId=1) — actively growing, can divide
  • Hypoxic (TypeId=2) — reduced activity, does not grow
  • Necrotic (TypeId=3) — dead, shrinks and may be removed after a lifetime

• Oxygen field:

  • DiffusionSolverFE provides a global Oxygen field with boundary planes held at concentration 1.0.
  • Cells consume oxygen via Michaelis–Menten uptake (per-type uptake parameters in the XML).
  • Two threshold rules drive phenotype transitions (parameters in UserParameters):
    • O2_Thresh_NormoxicHypoxic (default 0.15)
    • O2_Thresh_HypoxicNecrotic (default 0.05)

• Fate and growth:

  • O2DrivenFateSteppable samples oxygen at each cell's center-of-mass and switches types according to thresholds.
  • Normoxic cells grow their targetVolume deterministically by GrowthRateNormoxic per MCS and update targetSurface accordingly.
  • Hypoxic cells do not grow but keep targets unchanged.
  • Necrotic cells shrink at NecroticShrinkageRate and are removed probabilistically after NecroticLifetime MCS.

• Mitosis:

  • Implemented in O2MitosisSteppable: when a cell's targetVolume reaches FinalTargetVolume (default 63), it may divide with probability DivProbNormoxic.
  • Post-mitosis the parent and child targets are split equally and surfaces recomputed.

• Radiotherapy (optional):

  • RadiotherapySteppable applies external-beam fractions using a linear-quadratic survival model controlled by RT_* parameters in XML (RT_Enable, RT_DoseGy, RT_Alpha, RT_Beta, RT_StartMCS, RT_PeriodMCS, RT_Fractions).

• Center compaction:

  • CenterCompactionSteppable applies an inward force (CenterPushStrength) to compact the spheroid toward the domain center.

• Analysis:

  • LightAnalysisSteppable provides simple plots for total volume and cell counts (Normoxic/Hypoxic/Necrotic) and logs oxygen statistics periodically.

Important parameters (found in mitosis_O2.xml UserParameters)

• InitialCellRadius (voxels) — starting sphere radius for the single seed cell. Default: 1.8
• FinalTargetVolume — target volume to trigger mitosis. Default: 63
• GrowthRateNormoxic — targetVolume increment per MCS for normoxic cells. Default: 1.95
• LambdaVolume*, LambdaSurface* — per-type constraint strengths
• O2_Thresh_NormoxicHypoxic, O2_Thresh_HypoxicNecrotic — oxygen thresholds for phenotype switching
• NecroticShrinkageRate, NecroticLifetime — necrotic cell dynamics
• CenterPushStrength — inward compaction force magnitude
• RT_* — radiotherapy controls (enable, dose, timing, alpha/beta)
• OutputFrequency — analysis/logging frequency

How to run

Notes:

• Parameters can be tweaked directly in mitosis_O2.xml under <UserParameters>; the steppables read those values at start.
• Enable radiotherapy by setting RT_Enable to 1 and adjust RT_* parameters as needed.

Suggested experiments

• Vary InitialCellRadius and GrowthRateNormoxic to observe different spheroid growth rates.
• Toggle RT_Enable and test different fractionation schemes using RT_Fractions and RT_PeriodMCS.
• Adjust O2_Thresh_* values to probe sensitivity of necrotic core formation.

Notes and limitations

• This model uses spherical approximations for surface calculations and simplified per-cell mechanics. It is designed for demonstration and exploratory simulations, not for direct clinical predictions.
• The code assumes a 3D domain and uses COM-based sampling which may be noisy for very small cells; adjust InitialCellRadius accordingly.