SimpleOxygenBasedCellCycleModel.cpp

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*/

#include "SimpleOxygenBasedCellCycleModel.hpp"
#include "RandomNumberGenerator.hpp"
#include "ApoptoticCellProperty.hpp"
#include "CellPropertyRegistry.hpp"
#include "Exception.hpp"

SimpleOxygenBasedCellCycleModel::SimpleOxygenBasedCellCycleModel()
    : mCurrentHypoxicDuration(0.0),
      mHypoxicConcentration(0.4),
      mQuiescentConcentration(1.0),
      mCriticalHypoxicDuration(2.0)
{
    mCurrentHypoxiaOnsetTime = SimulationTime::Instance()->GetTime();
}

double SimpleOxygenBasedCellCycleModel::GetCurrentHypoxicDuration()
{
    return mCurrentHypoxicDuration;
}

double SimpleOxygenBasedCellCycleModel::GetCurrentHypoxiaOnsetTime()
{
    return mCurrentHypoxiaOnsetTime;
}

void SimpleOxygenBasedCellCycleModel::UpdateCellCyclePhase()
{
    // mG1Duration is set when the cell-cycle model is given a cell

    bool cell_is_apoptotic = mpCell->HasCellProperty<ApoptoticCellProperty>();

    if (!cell_is_apoptotic)
    {
        UpdateHypoxicDuration();

        // Get cell's oxygen concentration
        double oxygen_concentration = mpCell->GetCellData()->GetItem("oxygen");

        AbstractSimpleCellCycleModel::UpdateCellCyclePhase();

        if (mCurrentCellCyclePhase == G_ONE_PHASE)
        {
            // Update G1 duration based on oxygen concentration
            double dt = SimulationTime::Instance()->GetTimeStep();

            if (oxygen_concentration < mQuiescentConcentration)
            {
                mG1Duration += (1 - std::max(oxygen_concentration, 0.0)/mQuiescentConcentration)*dt;
            }
        }
    }
}

AbstractCellCycleModel* SimpleOxygenBasedCellCycleModel::CreateCellCycleModel()
{
    // Create a new cell-cycle model
    SimpleOxygenBasedCellCycleModel* p_model = new SimpleOxygenBasedCellCycleModel();

    /*
     * Set each member variable of the new cell-cycle model that inherits
     * its value from the parent.
     *
     * Note 1: some of the new cell-cycle model's member variables (namely
     * mBirthTime, mCurrentCellCyclePhase, mReadyToDivide,
     * mCurrentHypoxicDuration, mCurrentHypoxiaOnsetTime) will already have been
     * correctly initialized in its constructor.
     *
     * Note 2: one or more of the new cell-cycle model's member variables
     * may be set/overwritten as soon as InitialiseDaughterCell() is called on
     * the new cell-cycle model.
     */
    p_model->SetBirthTime(mBirthTime);
    p_model->SetDimension(mDimension);
    p_model->SetMinimumGapDuration(mMinimumGapDuration);
    p_model->SetStemCellG1Duration(mStemCellG1Duration);
    p_model->SetTransitCellG1Duration(mTransitCellG1Duration);
    p_model->SetSDuration(mSDuration);
    p_model->SetG2Duration(mG2Duration);
    p_model->SetMDuration(mMDuration);
    p_model->SetHypoxicConcentration(mHypoxicConcentration);
    p_model->SetQuiescentConcentration(mQuiescentConcentration);
    p_model->SetCriticalHypoxicDuration(mCriticalHypoxicDuration);
    p_model->SetCurrentHypoxiaOnsetTime(mCurrentHypoxiaOnsetTime);

    return p_model;
}

void SimpleOxygenBasedCellCycleModel::UpdateHypoxicDuration()
{
    assert(!(mpCell->HasCellProperty<ApoptoticCellProperty>()));
    assert(!mpCell->HasApoptosisBegun());

    // Get cell's oxygen concentration
    double oxygen_concentration = mpCell->GetCellData()->GetItem("oxygen");

    if (oxygen_concentration < mHypoxicConcentration)
    {
        // Update the duration of the current period of hypoxia
        mCurrentHypoxicDuration = (SimulationTime::Instance()->GetTime() - mCurrentHypoxiaOnsetTime);

        // Include a little bit of stochasticity here
        double prob_of_death = 0.9 - 0.5*(oxygen_concentration/mHypoxicConcentration);
        if (mCurrentHypoxicDuration > mCriticalHypoxicDuration && RandomNumberGenerator::Instance()->ranf() < prob_of_death)
        {
            /*
             * This method is usually called within a CellBasedSimulation, after the CellPopulation
             * has called CellPropertyRegistry::TakeOwnership(). This means that were we to call
             * CellPropertyRegistry::Instance() here when adding the ApoptoticCellProperty, we would
             * be creating a new CellPropertyRegistry. In this case the ApoptoticCellProperty cell
             * count would be incorrect. We must therefore access the ApoptoticCellProperty via the
             * cell's CellPropertyCollection.
             */
            boost::shared_ptr<AbstractCellProperty> p_apoptotic_property =
                mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<ApoptoticCellProperty>();
            mpCell->AddCellProperty(p_apoptotic_property);
        }
    }
    else
    {
        // Reset the cell's hypoxic duration and update the time at which the onset of hypoxia occurs
        mCurrentHypoxicDuration = 0.0;
        mCurrentHypoxiaOnsetTime = SimulationTime::Instance()->GetTime();
    }
}

double SimpleOxygenBasedCellCycleModel::GetHypoxicConcentration()
{
    return mHypoxicConcentration;
}

void SimpleOxygenBasedCellCycleModel::SetHypoxicConcentration(double hypoxicConcentration)
{
    assert(hypoxicConcentration<=1.0);
    assert(hypoxicConcentration>=0.0);
    mHypoxicConcentration = hypoxicConcentration;
}

double SimpleOxygenBasedCellCycleModel::GetQuiescentConcentration()
{
    return mQuiescentConcentration;
}

void SimpleOxygenBasedCellCycleModel::SetQuiescentConcentration(double quiescentConcentration)
{
    assert(quiescentConcentration <= 1.0);
    assert(quiescentConcentration >= 0.0);
    mQuiescentConcentration = quiescentConcentration;
}

double SimpleOxygenBasedCellCycleModel::GetCriticalHypoxicDuration()
{
    return mCriticalHypoxicDuration;
}

void SimpleOxygenBasedCellCycleModel::SetCriticalHypoxicDuration(double criticalHypoxicDuration)
{
    assert(criticalHypoxicDuration >= 0.0);
    mCriticalHypoxicDuration = criticalHypoxicDuration;
}

void SimpleOxygenBasedCellCycleModel::SetCurrentHypoxiaOnsetTime(double currentHypoxiaOnsetTime)
{
    assert(currentHypoxiaOnsetTime >= 0.0);
    mCurrentHypoxiaOnsetTime = currentHypoxiaOnsetTime;
}

void SimpleOxygenBasedCellCycleModel::OutputCellCycleModelParameters(out_stream& rParamsFile)
{
    *rParamsFile << "\t\t\t<HypoxicConcentration>" << mHypoxicConcentration << "</HypoxicConcentration>\n";
    *rParamsFile << "\t\t\t<QuiescentConcentration>" << mQuiescentConcentration << "</QuiescentConcentration>\n";
    *rParamsFile << "\t\t\t<CriticalHypoxicDuration>" << mCriticalHypoxicDuration << "</CriticalHypoxicDuration>\n";

    // Call method on direct parent class
    AbstractSimpleCellCycleModel::OutputCellCycleModelParameters(rParamsFile);
}

// Serialization for Boost >= 1.36
#include "SerializationExportWrapperForCpp.hpp"
CHASTE_CLASS_EXPORT(SimpleOxygenBasedCellCycleModel)