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Session 9: s imulating transport processes and cell-cell signalling in Chaste. Cell-based Chaste workshop Friday 6 th January 2012. Summary of Delta-Notch model. In many developing tissues a fine-grained mixture of cell types is generated through cell-cell interactions
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Session 9: simulating transport processes and cell-cell signalling in Chaste Cell-based Chaste workshop Friday 6thJanuary 2012
Summary of Delta-Notch model • In many developing tissues a fine-grained mixture of cell types is generated through cell-cell interactions • This occurs within a population of cells that are initially equivalent in their developmental potential • The mechanism is based on lateral inhibition • Extensive genetic and biochemical studies have identified Notchas the receptor and the product of Delta as the corresponding ligand expressed in the cell delivering inhibition
Summary of Delta-Notch model • Collier et al. (1996) model
Implementation • Create a suitable cell population, e.g. a VertexBasedCellPopulation, using a DeltaNotchCellCycleModel • Overridden UpdateCellCyclePhase() method updates the current level of mean Delta among nearest neighbours according to CellwiseData, and uses this to solve the Delta/Notch ODE system over one mechanics timestep • Set up CellwiseData • Create a DeltaNotchOffLatticeSimulation • Overridden PostSolve() method computes, for each cell, the current level of Delta, Notch, and mean Delta among nearest neighbours, and stores these in CellwiseData
Implementation • Hierarchy of classes • PDE class, e.g. CellwiseSourcePde • Boundary condition class, e.g. ConstBoundaryCondition • These are associated in a PdeAndBoundaryConditions object • One or more PdeAndBoundaryConditionsobjects, together with the cell population, are associated in a CellBasedPdeHandler • Use AbstractCellBasedSimulation::mpCellBasedPdeHandler • Call SetCellBasedPdeHandler() on the simulation object • The PDE handler will call SolvePdeAndWriteResultsToFile() within PostSolve() • PDE solution is stored in CellwiseData • Set up CellwiseData at start of simulation • Use a cell-cycle model such as SimpleOxygenBasedCellCycleModel, which has access to the PDE solution via CellwiseData
Implementation • Documentation and further details of the class hierarchy are available on the wiki. • You will find the tutorials for this session here: • UserTutorials/RunningDeltaNotchSimulations • UserTutorials/RunningTumourSpheroidSimulations • These will guide you through the implementation of these models. • Further exercises are also suggested for those who are interested.