Created by: Duncan Martinson
Issue 259: Collective cell migration is not only a hallmark of cancer but also of developmental biology. In both fields, it remains unclear how the extracellular matrix (ECM) may establish and guide cell movement. The images above depict agent-based model (ABM) simulations which investigate dynamic, reciprocal interactions between the ECM and neural crest stem cells traveling from an embryonic structure that later becomes the spinal cord. Our mathematical model, which is described here, is inspired by experimental observations that suggest neural crest cells remodel an initially punctate fibronectin matrix over the course of migration. We use the ABM to evaluate whether such remodeling allows leading cells in a neural crest stream to efficiently communicate the history of their trajectories to trailing cells. Global sensitivity analysis and simulated under/overexpression experiments reveal that contact guidance, a mechanism by which cells align themselves along ECM fibers, is essential for robust long-distance migration along target corridors. In the images, which depict two example ABM simulations, fibronectin puncta and fibers are denoted by light blue squares and arrows, respectively, while neural crest cells are depicted as red and black circles (the only difference between the two cell types is that black agents can secrete new fibronectin).