LinearSpringWithVariableSpringConstantsForce.cpp

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#include "LinearSpringWithVariableSpringConstantsForce.hpp"
#include "MeshBasedCellPopulation.hpp"
#include "VanLeeuwen2009WntSwatCellCycleModelHypothesisOne.hpp"
#include "VanLeeuwen2009WntSwatCellCycleModelHypothesisTwo.hpp"
#include "ApoptoticCellProperty.hpp"

template<unsigned DIM>
LinearSpringWithVariableSpringConstantsForce<DIM>::LinearSpringWithVariableSpringConstantsForce()
    : GeneralisedLinearSpringForce<DIM>(),
      mUseEdgeBasedSpringConstant(false),
      mUseMutantSprings(false),
      mMutantMutantMultiplier(DOUBLE_UNSET),
      mNormalMutantMultiplier(DOUBLE_UNSET),
      mUseBCatSprings(false),
      mUseApoptoticSprings(false),
      mBetaCatSpringScaler(18.14/6.0), // scale spring constant with beta-catenin level (divided by 6 for heaxagonal cells)
      mApoptoticSpringTensionStiffness(15.0*0.25),
      mApoptoticSpringCompressionStiffness(15.0*0.75)
{
}

template<unsigned DIM>
LinearSpringWithVariableSpringConstantsForce<DIM>::~LinearSpringWithVariableSpringConstantsForce()
{
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::SetEdgeBasedSpringConstant(bool useEdgeBasedSpringConstant)
{
    assert(DIM == 2);
    mUseEdgeBasedSpringConstant = useEdgeBasedSpringConstant;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::SetMutantSprings(bool useMutantSprings, double mutantMutantMultiplier, double normalMutantMultiplier)
{
    mUseMutantSprings = useMutantSprings;
    mMutantMutantMultiplier = mutantMutantMultiplier;
    mNormalMutantMultiplier = normalMutantMultiplier;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::SetBetaCateninSprings(bool useBCatSprings)
{
    mUseBCatSprings = useBCatSprings;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::SetApoptoticSprings(bool useApoptoticSprings)
{
    mUseApoptoticSprings = useApoptoticSprings;
}

template<unsigned DIM>
double LinearSpringWithVariableSpringConstantsForce<DIM>::VariableSpringConstantMultiplicationFactor(
    unsigned nodeAGlobalIndex,
    unsigned nodeBGlobalIndex,
    AbstractCellPopulation<DIM>& rCellPopulation,
    bool isCloserThanRestLength)
{

    double multiplication_factor = GeneralisedLinearSpringForce<DIM>::VariableSpringConstantMultiplicationFactor(nodeAGlobalIndex,
                                                                                                            nodeBGlobalIndex,
                                                                                                            rCellPopulation,
                                                                                                            isCloserThanRestLength);

    CellPtr p_cell_A = rCellPopulation.GetCellUsingLocationIndex(nodeAGlobalIndex);
    CellPtr p_cell_B = rCellPopulation.GetCellUsingLocationIndex(nodeBGlobalIndex);

    /*
     * The next code block computes the edge-dependent spring constant as given by equation
     * (3) in the following reference: van Leeuwen et al. 2009. An integrative computational model
     * for intestinal tissue renewal. Cell Prolif. 42(5):617-636. doi:10.1111/j.1365-2184.2009.00627.x
     */
    if (mUseEdgeBasedSpringConstant)
    {
        assert(bool(dynamic_cast<MeshBasedCellPopulation<DIM>*>(&rCellPopulation)));
        assert(!mUseBCatSprings);   // don't want to do both (both account for edge length)

        multiplication_factor = (static_cast<MeshBasedCellPopulation<DIM>*>(&rCellPopulation))->GetVoronoiEdgeLength(nodeAGlobalIndex, nodeBGlobalIndex)*sqrt(3.0);
    }

    if (mUseMutantSprings)
    {
        unsigned number_of_mutants = 0;

        if (p_cell_A->GetMutationState()->IsType<ApcTwoHitCellMutationState>() || p_cell_A->GetMutationState()->IsType<BetaCateninOneHitCellMutationState>())
        {
            // If cell A is mutant
            number_of_mutants++;
        }

        if (p_cell_B->GetMutationState()->IsType<ApcTwoHitCellMutationState>() || p_cell_B->GetMutationState()->IsType<BetaCateninOneHitCellMutationState>())
        {
            // If cell B is mutant
            number_of_mutants++;
        }

        switch (number_of_mutants)
        {
            case 1u:
            {
                multiplication_factor *= mNormalMutantMultiplier;
                break;
            }
            case 2u:
            {
                multiplication_factor *= mMutantMutantMultiplier;
                break;
            }
        }
    }

    /*
     * The next code block computes the beta-catenin dependent spring constant as given by equation
     * (4) in the following reference: van Leeuwen et al. 2009. An integrative computational model
     * for intestinal tissue renewal. Cell Prolif. 42(5):617-636. doi:10.1111/j.1365-2184.2009.00627.x
     */
    if (mUseBCatSprings)
    {
        assert(bool(dynamic_cast<MeshBasedCellPopulation<DIM>*>(&rCellPopulation)));

        // If using beta-cat dependent springs, both cell-cycle models had better be VanLeeuwen2009WntSwatCellCycleModel
        AbstractVanLeeuwen2009WntSwatCellCycleModel* p_model_A = dynamic_cast<AbstractVanLeeuwen2009WntSwatCellCycleModel*>(p_cell_A->GetCellCycleModel());
        AbstractVanLeeuwen2009WntSwatCellCycleModel* p_model_B = dynamic_cast<AbstractVanLeeuwen2009WntSwatCellCycleModel*>(p_cell_B->GetCellCycleModel());

        assert(!mUseEdgeBasedSpringConstant);   // This already adapts for edge lengths - don't want to do it twice.
        double beta_cat_cell_1 = p_model_A->GetMembraneBoundBetaCateninLevel();
        double beta_cat_cell_2 = p_model_B->GetMembraneBoundBetaCateninLevel();

        MeshBasedCellPopulation<DIM>* p_static_cast_cell_population = (static_cast<MeshBasedCellPopulation<DIM>*>(&rCellPopulation));

        double perim_cell_1 = p_static_cast_cell_population->GetSurfaceAreaOfVoronoiElement(nodeAGlobalIndex);
        double perim_cell_2 = p_static_cast_cell_population->GetSurfaceAreaOfVoronoiElement(nodeBGlobalIndex);
        double edge_length_between_1_and_2 = p_static_cast_cell_population->GetVoronoiEdgeLength(nodeAGlobalIndex, nodeBGlobalIndex);

        double beta_cat_on_cell_1_edge = beta_cat_cell_1 *  edge_length_between_1_and_2 / perim_cell_1;
        double beta_cat_on_cell_2_edge = beta_cat_cell_2 *  edge_length_between_1_and_2 / perim_cell_2;

        double min_beta_Cat_of_two_cells = std::min(beta_cat_on_cell_1_edge, beta_cat_on_cell_2_edge);

        multiplication_factor *= min_beta_Cat_of_two_cells / mBetaCatSpringScaler;
    }

    if (mUseApoptoticSprings)
    {
        bool cell_A_is_apoptotic = p_cell_A->HasCellProperty<ApoptoticCellProperty>();
        bool cell_B_is_apoptotic = p_cell_B->HasCellProperty<ApoptoticCellProperty>();

        if (cell_A_is_apoptotic || cell_B_is_apoptotic)
        {
            double spring_a_stiffness = 2.0 * this->GetMeinekeSpringStiffness();
            double spring_b_stiffness = 2.0 * this->GetMeinekeSpringStiffness();

            if (cell_A_is_apoptotic)
            {
                if (!isCloserThanRestLength) // if under tension
                {
                    spring_a_stiffness = mApoptoticSpringTensionStiffness;
                }
                else // if under compression
                {
                    spring_a_stiffness = mApoptoticSpringCompressionStiffness;
                }
            }
            if (cell_B_is_apoptotic)
            {
                if (!isCloserThanRestLength) // if under tension
                {
                    spring_b_stiffness = mApoptoticSpringTensionStiffness;
                }
                else // if under compression
                {
                    spring_b_stiffness = mApoptoticSpringCompressionStiffness;
                }
            }

            multiplication_factor /= (1.0/spring_a_stiffness + 1.0/spring_b_stiffness)*this->GetMeinekeSpringStiffness();
        }
    }

    return multiplication_factor;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::AddForceContribution(AbstractCellPopulation<DIM>& rCellPopulation)
{
    // Throw an exception message if not using a MeshBasedCellPopulation
    if (dynamic_cast<MeshBasedCellPopulation<DIM>*>(&rCellPopulation) == NULL)
    {
        EXCEPTION("LinearSpringWithVariableSpringConstantsForce is to be used with a subclass of MeshBasedCellPopulation only");
    }

    MeshBasedCellPopulation<DIM>* p_static_cast_cell_population = static_cast<MeshBasedCellPopulation<DIM>*>(&rCellPopulation);

    for (typename MeshBasedCellPopulation<DIM>::SpringIterator spring_iterator = p_static_cast_cell_population->SpringsBegin();
        spring_iterator != p_static_cast_cell_population->SpringsEnd();
        ++spring_iterator)
    {
        unsigned nodeA_global_index = spring_iterator.GetNodeA()->GetIndex();
        unsigned nodeB_global_index = spring_iterator.GetNodeB()->GetIndex();

        c_vector<double, DIM> force = this->CalculateForceBetweenNodes(nodeA_global_index, nodeB_global_index, rCellPopulation);
        c_vector<double, DIM> negative_force = -1.0*force;

        spring_iterator.GetNodeB()->AddAppliedForceContribution(negative_force);
        spring_iterator.GetNodeA()->AddAppliedForceContribution(force);
    }
}

template<unsigned DIM>
double LinearSpringWithVariableSpringConstantsForce<DIM>::GetBetaCatSpringScaler()
{
    return mBetaCatSpringScaler;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::SetBetaCatSpringScaler(double betaCatSpringScaler)
{
    assert(betaCatSpringScaler > 0.0);
    mBetaCatSpringScaler = betaCatSpringScaler;
}

template<unsigned DIM>
double LinearSpringWithVariableSpringConstantsForce<DIM>::GetApoptoticSpringTensionStiffness()
{
    return mApoptoticSpringTensionStiffness;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::SetApoptoticSpringTensionStiffness(double apoptoticSpringTensionStiffness)
{
    assert(apoptoticSpringTensionStiffness >= 0.0);
    mApoptoticSpringTensionStiffness = apoptoticSpringTensionStiffness;
}

template<unsigned DIM>
double LinearSpringWithVariableSpringConstantsForce<DIM>::GetApoptoticSpringCompressionStiffness()
{
    return mApoptoticSpringCompressionStiffness;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::SetApoptoticSpringCompressionStiffness(double apoptoticSpringCompressionStiffness)
{
    assert(apoptoticSpringCompressionStiffness >= 0.0);
    mApoptoticSpringCompressionStiffness = apoptoticSpringCompressionStiffness;
}

template<unsigned DIM>
void LinearSpringWithVariableSpringConstantsForce<DIM>::OutputForceParameters(out_stream& rParamsFile)
{
    *rParamsFile << "\t\t\t<UseEdgeBasedSpringConstant>" << mUseEdgeBasedSpringConstant << "</UseEdgeBasedSpringConstant>\n";
    *rParamsFile << "\t\t\t<UseMutantSprings>" << mUseMutantSprings << "</UseMutantSprings>\n";
    *rParamsFile << "\t\t\t<MutantMutantMultiplier>" << mMutantMutantMultiplier << "</MutantMutantMultiplier>\n";
    *rParamsFile << "\t\t\t<NormalMutantMultiplier>" << mNormalMutantMultiplier << "</NormalMutantMultiplier>\n";
    *rParamsFile << "\t\t\t<UseBCatSprings>" << mUseBCatSprings << "</UseBCatSprings>\n";
    *rParamsFile << "\t\t\t<UseApoptoticSprings>" << mUseApoptoticSprings << "</UseApoptoticSprings>\n";
    *rParamsFile << "\t\t\t<BetaCatSpringScaler>" << mBetaCatSpringScaler << "</BetaCatSpringScaler>\n";
    *rParamsFile << "\t\t\t<ApoptoticSpringTensionStiffness>" << mApoptoticSpringTensionStiffness << "</ApoptoticSpringTensionStiffness>\n";
    *rParamsFile << "\t\t\t<ApoptoticSpringCompressionStiffness>" << mApoptoticSpringCompressionStiffness << "</ApoptoticSpringCompressionStiffness>\n";

    // Call method on direct parent class
    GeneralisedLinearSpringForce<DIM>::OutputForceParameters(rParamsFile);
}

template class LinearSpringWithVariableSpringConstantsForce<1>;
template class LinearSpringWithVariableSpringConstantsForce<2>;
template class LinearSpringWithVariableSpringConstantsForce<3>;


// Serialization for Boost >= 1.36
#include "SerializationExportWrapperForCpp.hpp"
EXPORT_TEMPLATE_CLASS_SAME_DIMS(LinearSpringWithVariableSpringConstantsForce)