3-D PhysiCell simulation of a hanging drop spheroid - deterministic necrosis model

This is Video S1 in Ghaffarizadeh et al. (2018). A higher-resolution (1080p) video can be streamed at https://www.youtube.com/watch?v=WMhYW9D4SqM

Paper: https://doi.org/10.1371/journal.pcbi.1005991

3-D agent-based simulation of a hanging drop spheroid experiment. In this simulation, cells immediately become necrotic wherever pO2 < 5 mmHg. This simulation was completed on a single HPC compute node (dual Xeon 6-core CPUs at 3.4 GHz), requiring 82 hours and 23 minutes to run (including data saves once per simulated hour). It took 66 hours and 56 minutes to simulate 17 days to the first ~1 million cells. Simulations without file I/O are significantly faster.

The tumor maintains its expected spherical symmetry until the end of the simulation, when the tumor nears the computational boundary and experiences higher oxygenation that drive non-spherical growth.

Legend:

Dark circles: cell nuclei

Green cells: Proliferating Ki67+ cells, prior to mitosis

Magenta cells: Proliferating Ki67+ cells, after mitosis

Red cells: Apoptotic cells (cleaved Caspase-3 positive)

Pale blue cells: Quiescent Ki67- cells

Brown cells: Necrotic cells

This work is based on PhysiCell, an open source 3-D modeling package for multicellular biology at http://PhysiCell.MathCancer.org.

Method: Demonstration of PhysiCell, an agent-based, lattice-free model. Cell velocities determined by balance of adhesive, repulsive, and motile forces. Each cell has a phenotypic state governed by stochastic processes derived from nonhomogeneous Poisson processes.

Software source: PhysiCell is available as open source at http://PhysiCell.MathCancer.org, http://PhysiCell.sf.net, and https://github.com/mathcancer/physicell/releases.