Epithelial Cell Migration: Model selection for mechanistic model development

项目总结

Project Summary The collective migration of cells is a central biological process for multicellular organisms. Collective migration of epithelial sheets to close the gap during wound healing is an excellent illustration of this phenomenon. Inappropriate migratory movements can result in impaired wound healing, as seen in chronic wounds and diabetic foot ulcers. While substantial research has been devoted to its study, we still lack a foundational understanding of what drives groups of cells to move coherently as curative therapies are still not available for unhealable chronic wounds. Bortz, Liu, and Dukic groups are working together to develop a model selection-based approach to reveal driving mechanisms that control collective cell migration. Thus the long-term mathematical goal is to develop and apply a computationally efficient and rigorously well-posed model selection methodology for spatio-temporal biological phenomena modeled by differential equations. Toward this end, we will pursue a synergistic experimental, mathematical, and statistical approach to develop feasible candidate models, design and carry out validating experiments, and select the best models to infer the dominant driving mechanisms. While we made a lot of progress in developing mathematical frameworks for modeling various cell migratory behaviors, a bottleneck for unlocking the potentials of our new approach is the limited throughput of cell migration assays due to the manual experiment setup, which is tedious and time-consuming. Moreover, pipetting by hand is error-prone and induces avoidable variability between experiments. ASSIST PLUS from Integra Biosciences is designed for semi-automated liquid handling for cell culture studies and drug treatments. Acquisition of this robotic system will enable us to conduct numerous experiments in a more robustly and accelerate our research project.