Death Training App for PhysiCell

Config Basics tab: input parameters common to all models (e.g., domain grid, simulation time, choice/frequency of outputs)
Microenvironment tab: microenvironment parameters that are model-specific
User Params tab: user parameters that are model-specific
Out: Cell Plots tab: output display of the cells
Out: Substrate Plots tab: output display of the substrates

Clicking the 'Run' button will use the specified parameters and start a simulation. When clicked, it creates an "Output" widget that can be clicked/expanded to reveal the progress (text) of the simulation. When the simulation generates output file(s), they can be visualized in the appropriate output tabs. The "Max" count in each output tab will be dynamically updated as those output files are generated by the running simulation. When the "Run" button is clicked, it toggles to a "Cancel" button that will terminate (not pause) the simulation.

1. Background

Cells do not keep growing and dividing forever. Eventually, they undergo cell death, in which cells lyse (burst)

and decay. PhysiCell supports two models of cell death: apoptosis and necrosis. Apoptosis is programmed

cell death, which contributes to regular growth and function. Necrosis, on the other hand, is unprogrammed

cell death due to injury or disease. PhysiCell users may choose the model(s) appropriate for their projects.

The apoptosis model has only 1 phase, called Apoptotic. It is modeled by the following equation:

$A$ (1)

r is the rate at which the cell exits the apoptotic stage. The apoptosis model does not involve any growth

in cell size, though cells do shrink afterwards. The necrosis model has 2 phases: the swelling phase and the

lysed phase. The cell is in the swelling phase and grows in size until it reaches a certain volume, at which

point it lyses (bursts). After lysis, the cell shrinks (and potentially calcifies), entering the lysed phase.

2 Parameters

2.1 Death Class

The death class stores basic death information for the simulation being run.

2.1.1 rates

Death rate is, as expected, the rate at which cells die in a model, measured in 1/min. The rates are stored as a vector, with one rate per model.

2.1.2 models

models is a vector containing the death models used in the simulation. The two possible models are apoptosis and necrosis. If a simulation uses both, then the two models are included in the models vector.

2.1.3 parameters

The parameters vector holds the death parameters for each model. These parameters are described in the next section.

2.1.4 dead

dead is a variable that is either ”true” or ”false” and exists for every cell. If this variable is true for a cell, that cell is dead.

2.1.5 current death model index

The current death model index is the index of the current death model for dead cells. The index either corresponds to the apoptotic model or the necrotic model.

2.2 Death Cycle Parameter

Death cycle parameters determine what conditions lead to cell death.

2.2.1 time units

The default time units in PhysiCell is minutes.

2.2.2 Unlysed fluid change rate

The unlysed fluid change rate is the rate of fluid change (cytoplasmic fluid) before cell lysis. It is measured in 1/min

2.2.3 Lysed fluid change rate

The lysed fluid change rate is the rate of fluid change (cytoplasmic fluid) after cell lysis (after cell death). It is measured in 1/min.

2.2.4 Cytoplasmic biomass change rate

In contrast with the two fluid change rates above, the cytoplasmic biomass change rate is the rate of degradation for solids in the cytoplasm other than the nucleus. It is also measured in 1/min.

2.2.5 Nuclear biomass change rate

The nuclear biomass change rate is the rate of degradation for nucleus solids. It is measured in 1/min

2.2.6 Calcification rate

Calcification is the deposition of calcium salts. In the body, this commonly occurs in the formation of bone,

but it also occurs as a result of cell death. In PhysiCell, calcification rate is measured in 1/min.

2.2.7 Relative rupture volume

Relative rupture volume is the amount by which the volume of a cell must change for it to lyse. It is dependent on the original volume of the cell.

Basic instructions

Modify parameters in the "Config Basics", "Microenvironment", "User Params", or "Cell Types" tabs. Click the "Run" button once you are ready.

To view the output results, click the "Out: Plots" tab, and move the slider bar to advance through simulation frames. Note that as the simulation runs, the "# cell frames" field will increase, so you can view more simulation frames.

If there are multiple substrates defined in the Microenvironment, you can select a different one from the drop-down widget in the Plots tab. You can also fix the colormap range of values.

Note that you can download full simulation data for further exploration in your tools of choice. And you can also generate an animation of the cells to play in the browser and, optionally, download as a video.

Config Basics tab: input parameters common to all models (e.g., domain grid, simulation time, choice/frequency of outputs)
Microenvironment tab: microenvironment parameters that are model-specific
User Params tab: user parameters that are model-specific
Out: Plots tab: output display of cells and substrates
Animate tab: generate an animation of cells

Clicking the 'Run' button will use the specified parameters and start a simulation. When clicked, it creates an "Output" widget that can be clicked/expanded to reveal the progress (text) of the simulation. When the simulation generates output files, they can be visualized in the "Out: Plots" tab. The "# cell frames" will be dynamically updated as those output files are generated by the running simulation. When the "Run" button is clicked, it toggles to a "Cancel" button that will terminate (not pause) the simulation.

About the software:

This model and cloud-hosted demo are part of the education and outreach for the IU Engineered nanoBIO Node and the NCI-funded cancer systems biology grant U01CA232137. The models are built using PhysiCell: a C++ framework for multicellular systems biology [1] for the core simulation engine and xml2jupyter [2] to create the graphical user interface (GUI).

Cite this work

Researchers should cite this work as follows:

Furkan Kurtoglu (2020), "Death Training App for PhysiCell," https://nanohub.org/resources/trdeath. (DOI: 10.21981/KC63-CC04).

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