CompuCell3D Model of Cell Migration Reproduces Chemotaxis

Abstract

Chemotaxis combines three processes: directional sensing, polarity reorientation and migration. Directed migration plays an important role in immune response, metastasis, wound healing and development. To describe chemotaxis, we extend a previously published computational model of a 3D single cell, that presents three compartments (lamellipodium, nucleus and cytoplasm), whose migration on a flat surface quantitatively describes experiments. The simulation is built in the framework of CompuCell3D, an environment based on the Cellular Potts Model. In our extension, we treat chemotaxis as a compound process rather than a response to a potential force. We propose robust protocols to measure cell persistence, drift speed, terminal speed, chemotactic efficiency, taxis time, and we analyse cell migration dynamics in the cell reference frame from position and polarization recordings through time. Our metrics can be applied to experimental results and allow quantitative comparison between simulations and experiments. We found that our simulated cells exhibit a trade-off between polarization stability and chemotactic efficiency. Specifically, we found that cells with lower protrusion forces and smaller lamellipodia exhibit an increased ability to undergo chemotaxis. We also noticed no significant change in cell movement due to external chemical gradient when analysing cell displacement in the cell reference frame. Our results demonstrate the importance of measuring cell polarity throughout the entire cell trajectory, and treating velocity quantities carefully when cell movement is diffusive at short time intervals. The simulation we developed is adequate to the development of new measurement protocols, and it helps paving the way to more complex multicellular simulations to model collective migration and their interaction with external fields, which are under development on this date.