PhysiCell: Extracellular Matrix Modeling

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

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.

ECM-based cell-cell communication

Modification of extracellular matrix (ECM) is an important method of multi-cellular communication. This simulator enables exploring a remodelable model of ECM using a leader-follower cell phenotype interaction model inspired by the cancer biology literature [1]. In general, how the speeds of signal generation and other parameters impact emergent results such as which form (if any) of collective migration (collective invasion, stigmergy, or both) emerge.

The ECM and leader-follower models are implemented in PhysiCell[2], an open source cell-based, multicellular 3-D modeling framework written in C++. More information can be found in [2] or at the PhysiCell website. The ECM is modeled as a set of small ECM elements, each having 3 locally averaged properities: fiber orientation, anisotropy, and density. There are two cell types: leader cells and follower cells. Leaders (shown in blue) can modify the ECM (generating the communication signal) but are not affected by the ECM, while the follower cells (yellow) are affected by the ECM by changes in motility (direction and/or speed) but cannot change it [3].

This model is available as a pre-print [3] with source code available here.

Exploring the model

You can follow these suggestions to familiarize yourself with the model.

1) Run this model using the default parameters. This will be produce the right hand side of the figure above

2) In the Cell Types tab, select leader cell from the Cell type drop-down (should be selected by default). In Custom Data, change Anisotropy_increase_rate to 0.001 and fiber_realignment_rate to 1. Run the simulation - this will decrease the collective behavior - eliminating collective invasion and leaving many followers in the center of the domain.

3) To further explore the model, navigate to the User Params) tab and change discrete_ECM_remodeling to 0 (t is the 10th variable from the bottom). Note now the ECM is instantly remodeled - generating strong, clear signals for followers to read (view the anisotropy field). Run the simulation - this will recover behavior similar to the default parameters and produce the left side of the figure included above.

4) Change default_cell_speed to 1.0 and then 0.10 (running between changes in parameter settings naturally) - producing stigmergy and a non-changing morphology.

5) Now, you can enjoy yourself changing other parameters and creating new responses.

Cite this work

Researchers should cite this work as follows:

John Metzcar, Ben Duggan, Randy Heiland, Daniel Matthew Murphy, Paul Macklin (2023), "PhysiCell: Extracellular Matrix Modeling," https://nanohub.org/resources/physicellecm. (DOI: 10.21981/MRCQ-M996).

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