University at Buffalo, The State University of New York, Buffalo, NY
"Computational modeling of cell migration in complex chemokine environments"
In recent decades, research on the active expression and regulatory effects of chemokines in cancer and immune cells has made the chemokine system an emerging target of immunotherapy. Alteration in chemokine environments is expected during immunotherapy, emphasizing the importance of understanding cell migration in complex chemokine environments. The complex signaling network formed by chemokines and cognate receptors regulates diverse tumor and immune cell activities, including leukocyte recruitment, angiogenesis, tumor growth, proliferation, and metastasis. We built 2D & 3D agent-based models with Compucell3D (a cellular Potts lattice-based model) to simulate the physiological response, especially cell migration, of tumor and immune cells towards complex chemokine settings. The 2D model is used to understand the mechanisms of cell chemotaxis, monomer-dimer equilibrium of certain chemokines, and competition between different pairs of chemokines and cognate receptors. The 3D model simulates and predicts an in vitro transwell experiment where cells have more realistic biomechanics of neighboring cells and tissue-mimic biomaterials. Using the models, we investigated how chemokine concentration, chemotactic force, environment composition, energy term that governs random walk, and membrane properties can influence cell migration. Results from this study will be used to build new agent-based models to simulate in vivo cancer pathology and therapy, considering cells, chemokines, and tissue microenvironments.
Additional authors: Michael B. Dwinell (1); Ashlee N. Ford Versypt (2) (1) Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, WI (2) Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY