Mitosis Steppable.

Mitosis steppable is described in great detail in “Python Scripting Manual” - see for example

https://pythonscriptingmanual.readthedocs.io/en/latest/mitosis.html?highlight=mitosis

but because of its importance we are including a copy of that description here.

In developmental simulations we often need to simulate cells which grow and divide. In earlier versions of CompuCell3D we had to write quite complicated plugin to do that which was quite cumbersome and unintuitive. The only advantage of the plugin was that mitosis was taking place immediately after the pixel copy which had triggered mitosis condition. This guaranteed that any cell which was supposed divide at any instance in the simulation, actually did. However, because state of the simulation is normally observed after completion of full a Monte Carlo Step, and not in the middle of MCS it makes actually more sense to implement Mitosis as a steppable. Let us examine the simplest simulation which involves mitosis. We start with a single cell and grow it. When cell reaches critical (doubling) volume it divides. We check if the cell has reached doubling volume at the end of each MCS. The folder containing this simulation is

Demos/CompuCellPythonTutorial/steppableBasedMitosis. The mitosis algorithm is implemented in Demos/CompuCellPythonTutorial/steppableBasedMitosis/Simulation/steppableBasedMitosisSteppables.py

File:

Demos/CompuCellPythonTutorial/steppableBasedMitosis/Simulation/steppableBasedMitosisSteppables.py

from PySteppables import *
from PySteppablesExamples import MitosisSteppableBase
import CompuCell

class VolumeParamSteppable(SteppableBasePy):
    def __init__(self, _simulator, _frequency=1):
        SteppableBasePy.__init__(self, _simulator, _frequency)

    def start(self):
        for cell in self.cellList:
            cell.targetVolume = 25
            cell.lambdaVolume = 2.0

    def step(self, mcs):
        for cell in self.cellList:
            cell.targetVolume += 1

class MitosisSteppable(MitosisSteppableBase):
    def __init__(self, _simulator, _frequency=1):
        MitosisSteppableBase.__init__(self, _simulator, _frequency)

        # 0 - parent child position will be randomized between mitosis event
        # negative integer - parent appears on the 'left' of the child
        # positive integer - parent appears on the 'right' of the child
        self.setParentChildPositionFlag(-1)

    def step(self, mcs):
        cells_to_divide = []
        for cell in self.cellList:
            if cell.volume > 50:
                cells_to_divide.append(cell)

        for cell in cells_to_divide:
            # to change mitosis mode leave one of the below lines uncommented
            self.divideCellRandomOrientation(cell)

    def updateAttributes(self):
        self.parentCell.targetVolume /= 2.0  # reducing parent target volume
        self.cloneParent2Child()

        if self.parentCell.type == self.CONDENSING:
            self.childCell.type = self.NONCONDENSING
        else:
            self.childCell.type = self.CONDENSING

Two steppables:`` VolumeParamSteppable`` and MitosisSteppable are the essence of the above simulation. The first steppable initializes volume constraint for all the cells present at T=0 MCS (only one cell) and then every 10 MCS (see the frequency with which VolumeParamSteppable in initialized to run - Demos/CompuCellPythonTutorial/steppableBasedMitosis/Simulation/steppableBasedMitosis.py) it increases target volume of cells, effectively causing cells to grow.

from steppableBasedMitosisSteppables import VolumeParamSteppable
volumeParamSteppable=VolumeParamSteppable(sim ,10)
steppableRegistry.registerSteppable(volumeParamSteppable)

from steppableBasedMitosisSteppables import MitosisSteppable
mitosisSteppable=MitosisSteppable(sim, 10)
steppableRegistry.registerSteppable(mitosisSteppable)

The second steppable checks every 10 MCS (we can, of course, run it every MCS) if cell has reached doubling volume of 50. If it did such cell is added to the list cells_to_divide. After construction of cells_to_divide is complete we iterate over this list and divide all the cells in it.

Warning

It is important to divide cells outside the loop where we iterate over entire cell inventory. If we keep dividing cells in this loop we are adding elements to the list over which we iterate over and this might have unwanted side effects. The solution is to use use list of cells to divide as we did in the example.

Notice that we call self.divideCellRandomOrientation(cell) function to divide cells. Other modes of division are available as well and they are as follows:

self.divideCellOrientationVectorBased(cell,1,0,0)
self.divideCellAlongMajorAxis(cell)
self.divideCellAlongMinorAxis(cell)

Notice that MitosisSteppable inherits MitosisSteppableBase class (defined in PySteppablesExamples.py).It is the base class which ensures that after we call any of the cell dividing function (e.g. divideCellRandomOrientation) CompuCell3D will automatically call updateAttributes function as well. updateAttributes function is very important and we must call it in order to ensure integrity and sanity of the simulation. During mitosis a new cell is created (accessed in Python as childCell – defined in MitosisSteppableBase - self.mitosisSteppable.childCell) and as such this cell is uninitialized. It does have default attributes (read-only) of a cell such as volume, surface (if we decide to use surface constraint or SurfaceTracker plugin) but all other parameters of such cell are set to default values. In our simulation we have been setting targetVolume and lambdaVolume individually for each cell. After mitosis childCell will need those parameters to be set as well. To make things more interesting, in our simulation we decided to change type of cell to be different than type of parent cell. In more complex simulations where cells have more attributes which are used in the simulation, we have to make sure that in the updateAttributes function childCell and its attributes get properly initialized. It is also very common practice to change attributes of parentCell after mitosis as well to account for the fact that parentCell is not the original parentCell from before the mitosis.

Note

If you specify orientation vector for the mitosis the actual division will take place along the line/plane perpendicular to this vector.

Note

The name of the function where we update attributes after mitosis has to be exactly updateAtttributes. If it is called differently CC3D will not call it automatically. We can of course call such function by hand, immediately we do the mitosis but this is not very elegant solution.