Documentation for Release 2024.1

Running Vertex Based Crypt Simulations

This tutorial is automatically generated from TestRunningVertexBasedCryptSimulationsTutorial.hpp at revision 66cf8dbe76c3. Note that the code is given in full at the bottom of the page.

Examples showing how to create, run and visualize vertex-based simulations on periodic meshes with different cell-cycle models

Introduction

In this tutorial we show how Chaste can be used to create, run and visualize vertex-based simulations. This mechanical model was originally proposed by T. Nagai and H. Honda, 2000, “A dynamic cell model for the formation of epithelial tissues”, Philosophical Magazine Part B 81:699-719, doi:10.1103/PhysRevLett.69.2013.

The test

As in previous cell-based Chaste tutorials, we begin by including the necessary header files.

#include <cxxtest/TestSuite.h>
#include "CheckpointArchiveTypes.hpp"
#include "AbstractCellBasedTestSuite.hpp"

The remaining header files define classes that will be used in the cell population simulation test. We have encountered some of these header files in previous cell-based Chaste tutorials.

#include "CellsGenerator.hpp"
#include "CryptCellsGenerator.hpp"
#include "WntConcentration.hpp"
#include "SloughingCellKiller.hpp"
#include "OffLatticeSimulation.hpp"
#include "SmartPointers.hpp"
#include "FakePetscSetup.hpp"

The next three header files define two different types of cell-cycle model, one with fixed cell-cycle times and one where the cell-cycle time depends on the Wnt concentration.

#include "FixedG1GenerationalCellCycleModel.hpp"
#include "SimpleWntCellCycleModel.hpp"

The next header file defines a helper class for generating a suitable mesh.

#include "HoneycombVertexMeshGenerator.hpp"

The next header file defines a helper class for generating a periodic vertex mesh.

#include "CylindricalHoneycombVertexMeshGenerator.hpp"

The next header file defines the class that simulates the evolution of a crypt CellPopulation for a vertex mesh.

#include "CryptSimulation2d.hpp"

The next header file defines a vertex-based CellPopulation class.

#include "VertexBasedCellPopulation.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.

#include "NagaiHondaForce.hpp"

In conjunction with the NagaiHondaForce, we choose to use a child class of AbstractTargetAreaModifier to model cell growth between divisions. Here, we use the SimpleTargetAreaModifier.

#include "SimpleTargetAreaModifier.hpp"

Next, we define the test class.

class TestRunningVertexBasedCryptSimulationsTutorial : public AbstractCellBasedTestSuite
{
public:

Test 1 - create a vertex-based crypt simulation

The first test generates a crypt, in which we use a cylindrical vertex mesh, give each cell a fixed cell-cycle model, and enforce sloughing at the top of the crypt.

    void TestVertexBasedCrypt()
    {

Create a cylindrical mesh, and get the cell location indices. To enforce periodicity at the left and right hand sides of the mesh, we use a subclass called Cylindrical2dMesh, which has extra methods for maintaining periodicity.

         CylindricalHoneycombVertexMeshGenerator generator(6, 9);
         boost::shared_ptr<Cylindrical2dVertexMesh> p_mesh = generator.GetCylindricalMesh();

Having created a mesh, we now create a std::vector of CellPtrs. To do this, we the CryptCellsGenerator helper class, which is templated over the type of cell model required (here FixedG1GenerationalCellCycleModel) and the dimension. We create an empty vector of cells and pass this into the method along with the mesh. The third argument ’true’ indicates that the cells should be assigned random birth times, to avoid synchronous division. The cells vector is populated once the method Generate is called. The last four arguments represent the height below which cells belong to generations 0, 1, 2, 3 and 4, respectively.

        std::vector<CellPtr> cells;
        CryptCellsGenerator<FixedG1GenerationalCellCycleModel> cells_generator;
        cells_generator.Generate(cells, p_mesh.get(), std::vector<unsigned>(), true, 1.0, 2.0, 3.0, 4.0);

Create a cell population, as before.

        VertexBasedCellPopulation<2> crypt(*p_mesh, cells);

Create a simulator as before (except setting a different output directory).

        CryptSimulation2d simulator(crypt);
        simulator.SetOutputDirectory("VertexCrypt");
        simulator.SetEndTime(0.1);

Before running the simulation, we add a one or more force laws, which determine the mechanics of the cell population. For this test, we use a NagaiHondaForce.

        MAKE_PTR(NagaiHondaForce<2>, p_force);
        simulator.AddForce(p_force);

We next add a child class of AbstractTargetAreaModifier to the simulation. This modifier assigns and updates target areas to each cell throughout the simulation, modelling cell growth between divisions. The target areas are in turn used by the force law to determine the pressure forces on each vertex.

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

Before running the simulation, we add a cell killer. This object dictates conditions under which cells die. For this test, we use a SloughingCellKiller, which kills cells above a certain height.

        double crypt_length = 6.0;
        MAKE_PTR_ARGS(SloughingCellKiller<2>, p_killer, (&crypt, crypt_length));
        simulator.AddCellKiller(p_killer);

To run the simulation, we call Solve().

        simulator.Solve();
    }

To visualize the results, open a new terminal, cd to the Chaste directory, then cd to anim. Then do: java Visualize2dVertexCells /tmp/$USER/testoutput/VertexCrypt/results_from_time_0. You may have to do: javac Visualize2dVertexCells.java beforehand to create the java executable.

When we visualize the results, we should see three colours of cells: a row of blue stem cells, 3 rows of yellow transit cells, and 5 rows of pink differentiated cells. Cells above 6.0 will be sloughed off immediately.

Test 2 - create a vertex-based crypt simulation with a simple wnt dependent cell-cycle model

The next test generates a crypt, in which we use a cylindrical vertex mesh, and impose a linearly decreasing concentration gradient of Wnt. Cells detect the level of Wnt at their centre and those that are in a region of sufficient Wnt are defined to be transit cells, whilst those above this Wnt threshold are defined to be differentiated. The cell cycle length of transit cells is then assigned randomly from a uniform distribution.

    void TestVertexBasedCryptWithSimpleWntCellCycleModel()
    {

Create a cylindrical mesh, and get the cell location indices, as before.

        CylindricalHoneycombVertexMeshGenerator generator(6, 9);
        boost::shared_ptr<Cylindrical2dVertexMesh> p_mesh = generator.GetCylindricalMesh();

Create a std::vector of CellPtrs. Generate cells, which are assigned a SimpleWntCellCycleModel using the CryptCellsGenerator. The final boolean argument ’true’ indicates to assign randomly chosen birth times.

        std::vector<CellPtr> cells;
        CryptCellsGenerator<SimpleWntCellCycleModel> cells_generator;
        cells_generator.Generate(cells, p_mesh.get(), std::vector<unsigned>(), true);

Create a cell population, as before.

        VertexBasedCellPopulation<2> crypt(*p_mesh, cells);

Define the crypt length; this will be used for sloughing and calculating the Wnt gradient.

        double crypt_length = 6.0;

Set up a WntConcentration object, as in the tutorial Running Mesh Based Simulations.

        WntConcentration<2>::Instance()->SetType(LINEAR);
        WntConcentration<2>::Instance()->SetCellPopulation(crypt);
        WntConcentration<2>::Instance()->SetCryptLength(crypt_length);

Create a simulator as before, and add a force law, the target area modifier and a sloughing cell killer to it.

        CryptSimulation2d simulator(crypt);
        simulator.SetOutputDirectory("VertexCryptWithSimpleWntCellCycleModel");
        simulator.SetEndTime(0.1);

        MAKE_PTR(NagaiHondaForce<2>, p_force);
        simulator.AddForce(p_force);

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

        MAKE_PTR_ARGS(SloughingCellKiller<2>, p_killer, (&crypt, crypt_length));
        simulator.AddCellKiller(p_killer);

Here we impose a boundary condition at the base: that cells at the bottom of the crypt are repelled if they move past 0.

        simulator.UseJiggledBottomCells();

Run the simulation, by calling Solve().

        simulator.Solve();
    }

To visualize the results, open a new terminal, cd to the Chaste directory, then cd to anim. Then do: java Visualize2dVertexCells /tmp/$USER/testoutput/VertexCryptWithSimpleWntCellCycleModel/results_from_time_0. You may have to do: javac Visualize2dVertexCells.java beforehand to create the java executable.

When we visualize the results, we should see two colours of cells: yellow transit cells and pink differentiated cells. Cells above 6.0 will be sloughed off immediately.

};

Full code

#include <cxxtest/TestSuite.h>
#include "CheckpointArchiveTypes.hpp"
#include "AbstractCellBasedTestSuite.hpp"

#include "CellsGenerator.hpp"
#include "CryptCellsGenerator.hpp"
#include "WntConcentration.hpp"
#include "SloughingCellKiller.hpp"
#include "OffLatticeSimulation.hpp"
#include "SmartPointers.hpp"
#include "FakePetscSetup.hpp"
#include "FixedG1GenerationalCellCycleModel.hpp"
#include "SimpleWntCellCycleModel.hpp"
#include "HoneycombVertexMeshGenerator.hpp"
#include "CylindricalHoneycombVertexMeshGenerator.hpp"
#include "CryptSimulation2d.hpp"
#include "VertexBasedCellPopulation.hpp"
#include "NagaiHondaForce.hpp"
#include "SimpleTargetAreaModifier.hpp"

class TestRunningVertexBasedCryptSimulationsTutorial : public AbstractCellBasedTestSuite
{
public:
    void TestVertexBasedCrypt()
    {
         CylindricalHoneycombVertexMeshGenerator generator(6, 9);
         boost::shared_ptr<Cylindrical2dVertexMesh> p_mesh = generator.GetCylindricalMesh();

        std::vector<CellPtr> cells;
        CryptCellsGenerator<FixedG1GenerationalCellCycleModel> cells_generator;
        cells_generator.Generate(cells, p_mesh.get(), std::vector<unsigned>(), true, 1.0, 2.0, 3.0, 4.0);

        VertexBasedCellPopulation<2> crypt(*p_mesh, cells);

        CryptSimulation2d simulator(crypt);
        simulator.SetOutputDirectory("VertexCrypt");
        simulator.SetEndTime(0.1);

        MAKE_PTR(NagaiHondaForce<2>, p_force);
        simulator.AddForce(p_force);

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

        double crypt_length = 6.0;
        MAKE_PTR_ARGS(SloughingCellKiller<2>, p_killer, (&crypt, crypt_length));
        simulator.AddCellKiller(p_killer);

        simulator.Solve();
    }

    void TestVertexBasedCryptWithSimpleWntCellCycleModel()
    {
        CylindricalHoneycombVertexMeshGenerator generator(6, 9);
        boost::shared_ptr<Cylindrical2dVertexMesh> p_mesh = generator.GetCylindricalMesh();

        std::vector<CellPtr> cells;
        CryptCellsGenerator<SimpleWntCellCycleModel> cells_generator;
        cells_generator.Generate(cells, p_mesh.get(), std::vector<unsigned>(), true);

        VertexBasedCellPopulation<2> crypt(*p_mesh, cells);

        double crypt_length = 6.0;

        WntConcentration<2>::Instance()->SetType(LINEAR);
        WntConcentration<2>::Instance()->SetCellPopulation(crypt);
        WntConcentration<2>::Instance()->SetCryptLength(crypt_length);

        CryptSimulation2d simulator(crypt);
        simulator.SetOutputDirectory("VertexCryptWithSimpleWntCellCycleModel");
        simulator.SetEndTime(0.1);

        MAKE_PTR(NagaiHondaForce<2>, p_force);
        simulator.AddForce(p_force);

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

        MAKE_PTR_ARGS(SloughingCellKiller<2>, p_killer, (&crypt, crypt_length));
        simulator.AddCellKiller(p_killer);

        simulator.UseJiggledBottomCells();

        simulator.Solve();
    }
};
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