Development of a Three-Dimensional Multiscale Agent-Based Tumor Model Simulating Gene-Prote.pdf

Le Zhang et al.: Development of a 3D Multiscale Agent-Based Tumor Model 1 Development of a Three-Dimensional Multiscale Agent-Based Tumor Model: Simulating Gene-Protein Interaction Profiles, Cell Phenotypes Multicellular Patterns in Brain Cancer Le Zhang 1, Chaitanya A. Athale 2 and Thomas S. Deisboeck 1* 1 Complex Biosystems Modeling Laboratory, Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA; 2 Cell Biology and Biophysics Department, European Molecular Biology Laboratory (EMBL), Heidelberg, D-69117, Germany. Running Title: Development of a 3D Multiscale Agent-Based Tumor Model Keywords: glioma, epidermal growth factor receptor, cell cycle, migration, proliferation, agent-based model. *Corresponding Author: Thomas S. Deisboeck, M.D. Complex Biosystems Modeling Laboratory Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital-East, 2301 Bldg. 149, 13th Street Charlestown, MA 02129 Tel: 617-724-1845 Fax: 617-726-7422 Email: deisboec@ Le Zhang et al.: Development of a 3D Multiscale Agent-Based Tumor Model 2 ABSTRACT Experimental evidence suggests that epidermal growth factor receptor (EGFR)-mediated activation of the signaling protein phospholipase Cγ plays a critical role in a cancer cell’s phenotypic decision to either proliferate or to migrate at a given point in time. Here, we present a novel three-dimensional multiscale agent-based model to simulate this cellular decision process in the context of a virtual brain tumor. Each tumor cell is equipped with an EGFR gene-protein interaction network module that also connects to a simplified cell cycle description. The simulation results show that over time proliferative and migratory cell populations not only oscillate but also directly impact the spatio-temporal expansion patterns of the entire