This tutorial is automatically generated from the file cell_based/test/tutorial/TestRunningDifferentialAdhesionSimulationsTutorial.hpp at revision 5e8c8d7218a9/git_repo. Note that the code is given in full at the bottom of the page.

An example showing how to simulate cell sorting due to differential adhesion in a vertex-based model

Introduction

In this tutorial we show how Chaste can be used to simulate a growing cell monolayer culture comprising two distinct cell types, which exhibit differential adhesion. We encountered a similar implementation in the second test in the TestRunningPottsBasedSimulationsTutorial?, which used a cellular Potts model of cell interactions; here we use a vertex-based model.

The test

As in previous tutorials, we begin by including the necessary header files. We have encountered these files already. Recall that often, either CheckpointArchiveTypes.hpp or CellBasedSimulationArchiver.hpp must be included the first Chaste header.

#include <cxxtest/TestSuite.h>
#include "CheckpointArchiveTypes.hpp"
#include "AbstractCellBasedTestSuite.hpp"
#include "HoneycombVertexMeshGenerator.hpp"
#include "CellsGenerator.hpp"
#include "FixedG1GenerationalCellCycleModel.hpp"
#include "CellLabel.hpp"
#include "DifferentiatedCellProliferativeType.hpp"
#include "VertexBasedCellPopulation.hpp"
#include "CellAgesWriter.hpp"
#include "CellVolumesWriter.hpp"
#include "CellMutationStatesCountWriter.hpp"
#include "CellProliferativePhasesWriter.hpp"
#include "CellProliferativeTypesCountWriter.hpp"
#include "CellProliferativePhasesCountWriter.hpp"
#include "OffLatticeSimulation.hpp"
#include "SmartPointers.hpp"
#include "FakePetscSetup.hpp"

The next header file defines a force law for describing the mechanical interactions between neighbouring cells in the cell population, subject to each vertex. This force law is a subclass of NagaiHondaForce, which we encountered in the TestRunningVertexBasedSimulationsTutorial, that allows for different adhesion energy parameter values depending on the types of interacting cells.

#include "NagaiHondaDifferentialAdhesionForce.hpp"

Similar to the NagaiHondaForce, this force law requires a child class of AbstractTargetAreaModifier which assigns target areas to each cell and updates this information in each time step. Here, we use the SimpleTargetAreaModifier.

#include "SimpleTargetAreaModifier.hpp"

Having included all the necessary header files, we proceed by defining the test class.

class TestRunningDifferentialAdhesionSimulationsTutorial : public AbstractCellBasedTestSuite
{
public:

In this test, we demonstrate how to simulate a heterotypic monolayer that incorporates differential adhesion, using a vertex-based approach. This may be compared with the second test in the TestRunningPottsBasedSimulationsTutorial?, which implements a similar simulation using a cellular Potts model.

    void TestVertexBasedDifferentialAdhesionSimulation()
    {

First we create a regular vertex mesh. Here we choose to set the value of the cell rearrangement threshold.

        HoneycombVertexMeshGenerator generator(5, 5);
        MutableVertexMesh<2,2>* p_mesh = generator.GetMesh();
        p_mesh->SetCellRearrangementThreshold(0.1);

We then create some cells using the helper class CellsGenerator. Note that in this simulation the cells are all differentiated, and thus no cell division occurs; if we wished, we could modify the three lines below in a straightforward manner to incorporate cell proliferation and investigate the effect of this on the cell sorting process.

        std::vector<CellPtr> cells;
        MAKE_PTR(DifferentiatedCellProliferativeType, p_diff_type);
        CellsGenerator<FixedG1GenerationalCellCycleModel, 2> cells_generator;
        cells_generator.GenerateBasic(cells, p_mesh->GetNumElements(), std::vector<unsigned>(), p_diff_type);

Using the vertex mesh and cells, we create a cell-based population object, and specify which results to output to file.

        VertexBasedCellPopulation<2> cell_population(*p_mesh, cells);
        cell_population.AddCellPopulationCountWriter<CellMutationStatesCountWriter>();
        cell_population.AddCellPopulationCountWriter<CellProliferativeTypesCountWriter>();
        cell_population.AddCellPopulationCountWriter<CellProliferativePhasesCountWriter>();
        cell_population.AddCellWriter<CellProliferativePhasesWriter>();
        cell_population.AddCellWriter<CellAgesWriter>();
        cell_population.AddCellWriter<CellVolumesWriter>();

We randomly label some cells using the cell property CellLabel. We begin by creating a shared pointer to this cell property using the helper singleton CellPropertyRegistry. We then loop over the cells and label each cell independently with probability 0.5. Note that since the cells have been passed to the VertexBasedCellPopulation object, the vector cells above is now empty, so we must use the Iterator to loop over cells.

         boost::shared_ptr<AbstractCellProperty> p_label(CellPropertyRegistry::Instance()->Get<CellLabel>());
        for (AbstractCellPopulation<2>::Iterator cell_iter = cell_population.Begin();
             cell_iter != cell_population.End();
             ++cell_iter)
        {
            if (RandomNumberGenerator::Instance()->ranf() < 0.5)
            {
                cell_iter->AddCellProperty(p_label);
            }
        }

We are now in a position to create and configure the cell-based simulation object. We can make the simulation run for longer to see more cell sorting by increasing the end time.

        OffLatticeSimulation<2> simulator(cell_population);
        simulator.SetOutputDirectory("TestVertexBasedDifferentialAdhesionSimulation");
        simulator.SetSamplingTimestepMultiple(10);
        simulator.SetEndTime(1.0);

Next we create the differential adhesion force law. This builds upon the model of Nagai, Honda and co-workers encounted in the TestRunningVertexBasedSimulationsTutorial? by allowing different values of the adhesion energy parameters depending on the types of two neighbouring cells. Here we interpret the 'type' of a cell as whether or not it has the cell property CellLabel; it would be straightforward to create a similar force law that took account of a cell's mutation state, for example. Having created the force law, we set the values of the parameters. If the adhesion energy for two neighbouring homotypic cells is less than that of two heterotypic cells, then we may expect cell sorting to occur, in which the cells of each type will tend to locally aggregate over time.

        MAKE_PTR(NagaiHondaDifferentialAdhesionForce<2>, p_force);
        p_force->SetNagaiHondaDeformationEnergyParameter(55.0);
        p_force->SetNagaiHondaMembraneSurfaceEnergyParameter(0.0);
        p_force->SetNagaiHondaCellCellAdhesionEnergyParameter(1.0);
        p_force->SetNagaiHondaLabelledCellCellAdhesionEnergyParameter(6.0);
        p_force->SetNagaiHondaLabelledCellLabelledCellAdhesionEnergyParameter(3.0);
        p_force->SetNagaiHondaCellBoundaryAdhesionEnergyParameter(12.0);
        p_force->SetNagaiHondaLabelledCellBoundaryAdhesionEnergyParameter(40.0);
        simulator.AddForce(p_force);

A NagaiHondaForceDifferentialAdhesionForce assumes that each cell has been assigned a target area. The SimpleTargetAreaModifier will assign and update the target areas of all cells.

        MAKE_PTR(SimpleTargetAreaModifier<2>, p_growth_modifier);
        simulator.AddSimulationModifier(p_growth_modifier);

Finally, we run the simulation.

        simulator.Solve();
    }

To visualize the results, use Paraview. See the UserTutorials/VisualizingWithParaview tutorial for more information.

Load the file /tmp/$USER/testoutput/TestVertexBasedDifferentialAdhesionSimulation/results_from_time_0/results.pvd.

};

Code

The full code is given below

File name `TestRunningDifferentialAdhesionSimulationsTutorial.hpp`

#include <cxxtest/TestSuite.h>
#include "CheckpointArchiveTypes.hpp"
#include "AbstractCellBasedTestSuite.hpp"
#include "HoneycombVertexMeshGenerator.hpp"
#include "CellsGenerator.hpp"
#include "FixedG1GenerationalCellCycleModel.hpp"
#include "CellLabel.hpp"
#include "DifferentiatedCellProliferativeType.hpp"
#include "VertexBasedCellPopulation.hpp"
#include "CellAgesWriter.hpp"
#include "CellVolumesWriter.hpp"
#include "CellMutationStatesCountWriter.hpp"
#include "CellProliferativePhasesWriter.hpp"
#include "CellProliferativeTypesCountWriter.hpp"
#include "CellProliferativePhasesCountWriter.hpp"
#include "OffLatticeSimulation.hpp"
#include "SmartPointers.hpp"
#include "FakePetscSetup.hpp"

#include "NagaiHondaDifferentialAdhesionForce.hpp"

#include "SimpleTargetAreaModifier.hpp"

class TestRunningDifferentialAdhesionSimulationsTutorial : public AbstractCellBasedTestSuite
{
public:

    void TestVertexBasedDifferentialAdhesionSimulation()
    {
        HoneycombVertexMeshGenerator generator(5, 5);
        MutableVertexMesh<2,2>* p_mesh = generator.GetMesh();
        p_mesh->SetCellRearrangementThreshold(0.1);

        std::vector<CellPtr> cells;
        MAKE_PTR(DifferentiatedCellProliferativeType, p_diff_type);
        CellsGenerator<FixedG1GenerationalCellCycleModel, 2> cells_generator;
        cells_generator.GenerateBasic(cells, p_mesh->GetNumElements(), std::vector<unsigned>(), p_diff_type);

        VertexBasedCellPopulation<2> cell_population(*p_mesh, cells);
        cell_population.AddCellPopulationCountWriter<CellMutationStatesCountWriter>();
        cell_population.AddCellPopulationCountWriter<CellProliferativeTypesCountWriter>();
        cell_population.AddCellPopulationCountWriter<CellProliferativePhasesCountWriter>();
        cell_population.AddCellWriter<CellProliferativePhasesWriter>();
        cell_population.AddCellWriter<CellAgesWriter>();
        cell_population.AddCellWriter<CellVolumesWriter>();

         boost::shared_ptr<AbstractCellProperty> p_label(CellPropertyRegistry::Instance()->Get<CellLabel>());
        for (AbstractCellPopulation<2>::Iterator cell_iter = cell_population.Begin();
             cell_iter != cell_population.End();
             ++cell_iter)
        {
            if (RandomNumberGenerator::Instance()->ranf() < 0.5)
            {
                cell_iter->AddCellProperty(p_label);
            }
        }

        OffLatticeSimulation<2> simulator(cell_population);
        simulator.SetOutputDirectory("TestVertexBasedDifferentialAdhesionSimulation");
        simulator.SetSamplingTimestepMultiple(10);
        simulator.SetEndTime(1.0);

        MAKE_PTR(NagaiHondaDifferentialAdhesionForce<2>, p_force);
        p_force->SetNagaiHondaDeformationEnergyParameter(55.0);
        p_force->SetNagaiHondaMembraneSurfaceEnergyParameter(0.0);
        p_force->SetNagaiHondaCellCellAdhesionEnergyParameter(1.0);
        p_force->SetNagaiHondaLabelledCellCellAdhesionEnergyParameter(6.0);
        p_force->SetNagaiHondaLabelledCellLabelledCellAdhesionEnergyParameter(3.0);
        p_force->SetNagaiHondaCellBoundaryAdhesionEnergyParameter(12.0);
        p_force->SetNagaiHondaLabelledCellBoundaryAdhesionEnergyParameter(40.0);
        simulator.AddForce(p_force);

        MAKE_PTR(SimpleTargetAreaModifier<2>, p_growth_modifier);
        simulator.AddSimulationModifier(p_growth_modifier);

        simulator.Solve();
    }

};

An example showing how to simulate cell sorting due to differential adhesion in a vertex-based model

Introduction

The test

Code

File name TestRunningDifferentialAdhesionSimulationsTutorial.hpp

File name `TestRunningDifferentialAdhesionSimulationsTutorial.hpp`