New Computer Program Simulates Cellular Behavior

Researchers from Indiana University, Johns Hopkins Medicine, the University of Maryland School of Medicine, and Oregon Health & Science University have created a computer program that replicates the dynamics of human and animal cells in any part of the body. Using mathematical analysis of cellular behavior, this software is intended to help scientists test and predict biological processes, drug responses, and cell interactions before resorting to costly experiments with live cells.

Results and simulations from the project are now detailed in Cell. The software, called PhysiCell, was originally developed to provide a mathematical and visual framework for modeling how cells behave according to their DNA, RNA, and environmental factors.

According to co-author Genevieve Stein-O’Brien, each cell is represented by a digital “agent” programmed to obey defined biological rules, allowing the simulation of tissue and organ formation, disease processes, and interactions with drugs or other cells. By virtually tracking these agents, the program can simulate processes such as tumor emergence, cancer-immune dynamics, and brain cell organization during development.

Unlike earlier modeling tools that required extensive expertise in mathematics and programming, PhysiCell introduces a new, accessible “grammar” for modeling. Paul Macklin of Indiana University, who helped create PhysiCell, noted, “It used to take months to write the code for these models, and now we can teach other scientists to create a basic immunology model in an hour or two.” Researchers can input simple, human-readable rules in an Excel spreadsheet—such as “this cell increases division as oxygen concentration increases”—which the software then turns into mathematical equations that govern simulated cell behavior.

This approach also enables integration of spatial transcriptomic data to map 3D organization of cells within tissues and study their function over time. Efforts led by Stein-O’Brien and other team members used data from the Allen Brain Atlas and human pancreatic tumors to construct simulations of both brain and cancer development.

A key validation experiment simulated how macrophages invade breast tumors by activating the EGFR pathway, which promotes cancer growth by increasing cancer cell mobility. Laboratory studies mirrored these findings, confirming the model’s predictive accuracy. The ongoing work aims to expand the program’s cellular behavior database and utilize artificial intelligence to automate the creation of new simulations.

Stein-O’Brien describes this initiative as a move toward a “virtual cell laboratory,” enabling researchers to use digital models as a preliminary step to prioritize hypotheses and refine experimental targets. By advancing digital replicas of biological processes, this technology has the potential to streamline and improve medical research.