ContactInhibitionCellCycleModel.cpp

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*/

#include "ContactInhibitionCellCycleModel.hpp"
#include "CellLabel.hpp"
#include "DifferentiatedCellProliferativeType.hpp"

ContactInhibitionCellCycleModel::ContactInhibitionCellCycleModel()
    : AbstractSimplePhaseBasedCellCycleModel(),
      mQuiescentVolumeFraction(DOUBLE_UNSET),
      mEquilibriumVolume(DOUBLE_UNSET),
      mCurrentQuiescentOnsetTime(SimulationTime::Instance()->GetTime()),
      mCurrentQuiescentDuration(0.0)
{
}

ContactInhibitionCellCycleModel::ContactInhibitionCellCycleModel(const ContactInhibitionCellCycleModel& rModel)
    : AbstractSimplePhaseBasedCellCycleModel(rModel),
      mQuiescentVolumeFraction(rModel.mQuiescentVolumeFraction),
      mEquilibriumVolume(rModel.mEquilibriumVolume),
      mCurrentQuiescentOnsetTime(rModel.mCurrentQuiescentOnsetTime),
      mCurrentQuiescentDuration(rModel.mCurrentQuiescentDuration)
{
    /*
     * Initialize only those member variables defined in this class.
     *
     * The member variables mCurrentCellCyclePhase, mG1Duration,
     * mMinimumGapDuration, mStemCellG1Duration, mTransitCellG1Duration,
     * mSDuration, mG2Duration and mMDuration are initialized in the
     * AbstractPhaseBasedCellCycleModel constructor.
     *
     * The member variables mBirthTime, mReadyToDivide and mDimension
     * are initialized in the AbstractCellCycleModel constructor.
     *
     * Note that mG1Duration is (re)set as soon as InitialiseDaughterCell()
     * is called on the new cell-cycle model.
     */
}

void ContactInhibitionCellCycleModel::UpdateCellCyclePhase()
{
    if ((mQuiescentVolumeFraction == DOUBLE_UNSET) || (mEquilibriumVolume == DOUBLE_UNSET))
    {
        EXCEPTION("The member variables mQuiescentVolumeFraction and mEquilibriumVolume have not yet been set.");
    }

    // Get cell volume
    double cell_volume = mpCell->GetCellData()->GetItem("volume");

    // Removes the cell label
    mpCell->RemoveCellProperty<CellLabel>();

    if (mCurrentCellCyclePhase == G_ONE_PHASE)
    {
        // Update G1 duration based on cell volume
        double dt = SimulationTime::Instance()->GetTimeStep();
        double quiescent_volume = mEquilibriumVolume * mQuiescentVolumeFraction;

        if (cell_volume < quiescent_volume)
        {
            // Update the duration of the current period of contact inhibition.
            mCurrentQuiescentDuration = SimulationTime::Instance()->GetTime() - mCurrentQuiescentOnsetTime;
            mG1Duration += dt;

            /*
             * 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 CellLabel, we would be creating
             * a new CellPropertyRegistry. In this case the CellLabel's cell count would be incorrect.
             * We must therefore access the CellLabel via the cell's CellPropertyCollection.
             */
            boost::shared_ptr<AbstractCellProperty> p_label =
                mpCell->rGetCellPropertyCollection().GetCellPropertyRegistry()->Get<CellLabel>();
            mpCell->AddCellProperty(p_label);
        }
        else
        {
            // Reset the cell's quiescent duration and update the time at which the onset of quiescent occurs
            mCurrentQuiescentDuration = 0.0;
            mCurrentQuiescentOnsetTime = SimulationTime::Instance()->GetTime();
        }
    }

    double time_since_birth = GetAge();
    assert(time_since_birth >= 0);

    if (mpCell->GetCellProliferativeType()->IsType<DifferentiatedCellProliferativeType>())
    {
        mCurrentCellCyclePhase = G_ZERO_PHASE;
    }
    else if (time_since_birth < GetMDuration())
    {
        mCurrentCellCyclePhase = M_PHASE;
    }
    else if (time_since_birth < GetMDuration() + mG1Duration)
    {
        mCurrentCellCyclePhase = G_ONE_PHASE;
    }
    else if (time_since_birth < GetMDuration() + mG1Duration + GetSDuration())
    {
        mCurrentCellCyclePhase = S_PHASE;
    }
    else if (time_since_birth < GetMDuration() + mG1Duration + GetSDuration() + GetG2Duration())
    {
        mCurrentCellCyclePhase = G_TWO_PHASE;
    }
}

AbstractCellCycleModel* ContactInhibitionCellCycleModel::CreateCellCycleModel()
{
    return new ContactInhibitionCellCycleModel(*this);
}

void ContactInhibitionCellCycleModel::SetQuiescentVolumeFraction(double quiescentVolumeFraction)
{
    mQuiescentVolumeFraction = quiescentVolumeFraction;
}

double ContactInhibitionCellCycleModel::GetQuiescentVolumeFraction() const
{
    return mQuiescentVolumeFraction;
}

void ContactInhibitionCellCycleModel::SetEquilibriumVolume(double equilibriumVolume)
{
    mEquilibriumVolume = equilibriumVolume;
}

double ContactInhibitionCellCycleModel::GetEquilibriumVolume() const
{
    return mEquilibriumVolume;
}

double ContactInhibitionCellCycleModel::GetCurrentQuiescentDuration() const
{
    return mCurrentQuiescentDuration;
}

double ContactInhibitionCellCycleModel::GetCurrentQuiescentOnsetTime() const
{
    return mCurrentQuiescentOnsetTime;
}

void ContactInhibitionCellCycleModel::OutputCellCycleModelParameters(out_stream& rParamsFile)
{
    *rParamsFile << "\t\t\t<QuiescentVolumeFraction>" << mQuiescentVolumeFraction << "</QuiescentVolumeFraction>\n";
    *rParamsFile << "\t\t\t<EquilibriumVolume>" << mEquilibriumVolume << "</EquilibriumVolume>\n";

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

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