Secretion / SecretionLocalFlex Plugin

Secretion “by cell type” can and should be handled by the appropriate PDE solver. To implement secretion in individual cells using Python we can use secretion plugin defined in the CC3DML as:

<Plugin Name="Secretion"/>

or as:

<Plugin Name="SecretionLocalFlex"/>

The inclusion of the above code in the CC3DML will allow users to implement secretion for individual cells from Python.

Note

Secretion for individual cells invoked via Python will be called only once per MCS.

Warning

Secretion plugin can be used to implement secretion by cell type however we strongly advise against doing so. Defining secretion by cell type in the Secretion plugin will lead to performance degradation on multi-core machines. Please see section below for more information if you are still interested in using secretion by cell-type inside Secretion plugin

Typical use of secretion from Python is demonstrated best in the example below:

class SecretionSteppable(SecretionBasePy):
    def __init__(self, _simulator, _frequency=1):
        SecretionBasePy.__init__(self, _simulator, _frequency)

    def step(self, mcs):
        attrSecretor = self.getFieldSecretor("ATTR")
        for cell in self.cellList:
            if cell.type == 3:
                attrSecretor.secreteInsideCell(cell, 300)
                attrSecretor.secreteInsideCellAtBoundary(cell, 300)
                attrSecretor.secreteOutsideCellAtBoundary(cell, 500)
                attrSecretor.secreteInsideCellAtCOM(cell, 300)
            elif cell.type == 2:
                attrSecretor.secreteInsideCellConstantConcentration(cell, 300)

Note

Instead of using SteppableBasePy class we are using SecretionBasePy class. The reason for this is that in order for secretion plugin with secretion modes accessible from Python to behave exactly as previous versions of PDE solvers (where secretion was done first followed by the “diffusion” step) we have to ensure that secretion steppable implemented in Python is called before each Monte Carlo Step, which implies that it will be also called before “diffusing” function of the PDE solvers. SecretionBasePy sets extra flag which ensures that steppable which inherits from SecretionBasePy is called before MCS (and before all “regular” Python steppables).

There is no magic to SecretionBasePy - if you still want to use SteppableBasePy as a base class for secretion do so, but remember that you need to set flag:

self.runBeforeMCS=1

to ensure that your new steppable will run before each MCS. See example below for alternative implementation of SecretionSteppable using SteppableBasePy as a base class:

class SecretionSteppable(SteppableBasePy):
    def __init__(self,_simulator,_frequency=1):
        SteppableBasePy.__init__(self,_simulator, _frequency)
        self.runBeforeMCS=1
    def step(self,mcs):
        attrSecretor=self.getFieldSecretor("ATTR")
        for cell in self.cellList:
            if cell.type==3:
                attrSecretor.secreteInsideCell(cell,300)
                attrSecretor.secreteInsideCellAtBoundary(cell,300)
                attrSecretor.secreteOutsideCellAtBoundary(cell,500)
                attrSecretor.secreteOutsideCellAtBoundaryOnContactwith(cell,500,[2,3])
                attrSecretor.secreteInsideCellAtCOM(cell,300)
                attrSecretor.uptakeInsideCellAtCOM(cell,300,0.2)
            elif cell.type==2:
                attrSecretor.secreteInsideCellConstantConcentration(cell,300)

The secretion of individual cells is handled through FieldSecretor objects. FieldSecretor concept is quite convenient because the amount of Python coding is quite small. To secrete chemical (this is now done for individual cell) we first create field secretor object:

attrSecretor = self.getFieldSecretor("ATTR")

which allows us to secrete into field called ATTR.

Then we pick a cell and using field secretor we simulate secretion of chemical ATTR by a cell:

attrSecretor.secreteInsideCell(cell,300)

Currently we support 7 secretion modes for individual cells:

  1. secreteInsideCell – this is equivalent to secretion in every pixel belonging to a cell

  2. secreteInsideCellConstantConcentration – this is equivalent to secretion in every pixel belonging to a cell and setting concentration to fixed, constant level

  3. secreteInsideCellAtBoundary – secretion takes place in the pixels belonging to the cell boundary

  4. secreteInsideCellAtBoundaryOnContactWith - secretion takes place in the pixels belonging to the cell boundary that touches any of the cells listed as the last argument of the function call

  5. secreteOutsideCellAtBoundary – secretion takes place in pixels which are outside the cell but in contact with cell boundary pixels

  6. secreteOutsideCellAtBoundaryOnContactWith - secretion takes place in pixels which are outside the cell but in contact with cell boundary pixels and in contact with cells listed the last argument of the function call

  7. secreteInsideCellAtCOM – secretion at the center of mass of the cell

and 6 uptake modes:

  1. uptakeInsideCell – this is equivalent to uptake in every pixel belonging to a cell

  2. uptakeInsideCellAtBoundary – uptake takes place in the pixels belonging to the cell boundary

  3. uptakeInsideCellAtBoundaryOnContactWith - uptake takes place in the pixels belonging to the cell boundary that touches any of the cells listed as the last argument of the function call

  4. uptakeOutsideCellAtBoundary – uptake takes place in pixels which are outside the cell but in contact with cell boundary pixels

  5. uptakeOutsideCellAtBoundaryOnContactWith - uptake takes place in pixels which are outside the cell but in contact with cell boundary pixels and in contact with cells listed the last argument of the function call

  6. uptakeInsideCellAtCOM – uptake at the center of mass of the cell

Secretion functions use the following syntax:

secrete*(cell,amount,list_of_cell_types)

Note

The list_of_cell_types is used only for function which implement such functionality i.e. secreteInsideCellAtBoundaryOnContactWith and secreteOutsideCellAtBoundaryOnContactWith

Uptake functions use the following syntax:

uptake*(cell,max_amount,relative_uptake,list_of_cell_types)

Note

The list_of_cell_types is used only for function which implement such functionality i.e. uptakeInsideCellAtBoundaryOnContactWith and uptakeOutsideCellAtBoundaryOnContactWith

Note

Important: The uptake works as follows: when available concentration is greater than max_amount, then max_amount is subtracted from current_concentration, otherwise we subtract relative_uptake*current_concentration.

As you may infer from above, the modes 1-5 require tracking of pixels belonging to cell and pixels belonging to cell boundary. If you are not using those secretion modes you may disable pixel tracking by including:

<DisablePixelTracker/>

or

<DisableBoundaryPixelTracker/>

as shown in the example below:

<Plugin Name="Secretion">

    <DisablePixelTracker/>
    <DisableBoundaryPixelTracker/>

    <Field Name="ATTR" ExtraTimesPerMC=”2”>
        <Secretion Type="Bacterium">200</Secretion>
        <SecretionOnContact Type="Medium" SecreteOnContactWith="B">300</SecretionOnContact>
        <ConstantConcentration Type="Bacterium">500</ConstantConcentration>
    </Field>
</Plugin>

Note

Make sure that fields into which you will be secreting chemicals exist. They are usually fields defined in PDE solvers. When using secretion plugin you do not need to specify SecretionData section for the PDE solvers.

When implementing e.g. secretion inside cell when the cell is in contact with other cell we use neighbor tracker and a short script in the spirit of the below snippet:

for cell in self.cellList:
    attrSecretor = self.getFieldSecretor("ATTR")
    for neighbor, commonSurfaceArea in self.getCellNeighborDataList(cell):
        if neighbor.type in [self.WALL]:
            attrSecretor.secreteInsideCell(cell, 300)

Secretion Plugin (legacy version)

Warning

While we still support Secretion plugin as described in this section we observed performance degradation when when declaring <Field> elements inside the plugin. To resolve this issue we encourage users to implement secretion “by cell type” in the PDE solver and keep using secretion plugin to implement secretion on a per-cell basis using Python scripting.

Note

In version 3.6.2 Secretion plugin should not be used with DiffusionSolverFE or any of the GPU-based solvers.

In earlier version os of CC3D secretion was part of PDE solvers. We still support this mode of model description however, starting in 3.5.0 we developed separate plugin which handles secretion only. Via secretion plugin we can simulate cellular secretion of various chemicals. The secretion plugin allows users to specify various secretion modes in the CC3DML file – CC3DML syntax is practically identical to the SecretionData syntax of PDE solvers. In addition to this Secretion plugin allows users to manipulate secretion properties of individual cells from Python level. To account for possibility of PDE solver being called multiple times during each MCS, the Secretion plugin can be called multiple times in each MCS as well. We leave it up to user the rescaling of secretion constants when using multiple secretion calls in each MCS.

Note

Secretion for individual cells invoked via Python will be called only once per MCS.

Typical CC3DML syntax for Secretion plugin is presented below:

<Plugin Name="Secretion">
    <Field Name="ATTR" ExtraTimesPerMC=”2”>
        <Secretion Type="Bacterium">200</Secretion>
        <SecretionOnContact Type="Medium" SecreteOnContactWith="B">300</SecretionOnContact>
        <ConstantConcentration Type="Bacterium">500</ConstantConcentration>
    </Field>
</Plugin>

By default ExtraTimesPerMC is set to 0 - meaning no extra calls to Secretion plugin per MCS.

Typical use of secretion from Python is demonstrated best in the example below:

class SecretionSteppable(SecretionBasePy):
    def __init__(self, _simulator, _frequency=1):
        SecretionBasePy.__init__(self, _simulator, _frequency)

    def step(self, mcs):
        attrSecretor = self.getFieldSecretor("ATTR")
        for cell in self.cellList:
            if cell.type == 3:
                attrSecretor.secreteInsideCell(cell, 300)
                attrSecretor.secreteInsideCellAtBoundary(cell, 300)
                attrSecretor.secreteOutsideCellAtBoundary(cell, 500)
                attrSecretor.secreteInsideCellAtCOM(cell, 300)