Agent-based modeling of cell-matrix interactions

Cell-populated extracellular matrix gels were one of the first approaches to tissue engineering and they are still used in this context. In addition, cell-populated gels are used as in vitro experimental models to explore in vivo processes such as tissue development and wound healing. A number of mathematical and computational models have been developed to describe cell-populated matrix gels. A limitation of many these models, however, is that they cannot explicitly handle the dynamic nature of cell-matrix interactions where cell repetitively bind to matrix, exert traction, and release. Agent-based modeling is ideally suited for handling dynamic processes, but has not previously been applied to cell-populated matrix gels. After introducing the concepts of agent-based modeling, an agent-based model of cell-populated matrix gels will be presented. This model incorporates basic mechanical interactions (e.g., Hookean and torsional springs) between multiple agents to model the behavior of individual ECM fibers, fiber networks, and cell-matrix interactions. This model makes a number of predictions that accurately reproduce experimental observations including the global and intercellular compaction of matrix, the preferential alignment of matrix fibers between pairs of cells, as well as directional cell migration in response to a stiffness gradient. Importantly, the model was not constructed to generate these experimentally consistent predictions, but instead these predictions were emergent behaviors arising from the simple mechanically based rules. In addition to reproducing experimental observations, the model provides insight into various cell-mediated processes including durotaxis, the ability of cells to migrate up a stiffness gradient.

Sponsored by the IMAG/MSM Cell-to-Macroscale Working Group,

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Keith J. Gooch, Dept. of Biomedical Engineering, The Ohio State University