Cell migration is key to many biological processes including embryonic development, wound healing, and disease progression. To create a unified theoretical framework for cell migration, we have now developed and experimentally tested a whole cell migration simulator based on the motor-clutch model of cellular force transmission by imposing coupled force balances and mass balances on molecular motors, adhesion molecules ("clutches"), and actin subunits in a compliant microenvironment. A relatively poorly understood aspect of cell migration is how microtubules control and influence the motor-clutch system. Using an integrated modeling-experimental approach, we are able to identify both convergent and divergent effects of the widely used anticancer drugs paclitaxel and vinblastine, both of which potently influence microtubule assembly dynamics (convergent effects) but work in opposite direction on influencing net microtubule assembly (divergent effects). We find that the motor-clutch cell migration simulator provides a theoretical framework with which to predict cell adhesion and migration in defined mechanochemical microenvironments in 1D, 2D, and 3D, and identify the key control points for microtubule-based on control on the system. We are applying the cell migration simulator to the case of glioblastoma specifically, where invasive cell migration drives a very poor prognosis, with median survival of 15 months and 5 year survival of less than 10%.

Bio:

David Odde is a professor of biomedical engineering at the University of Minnesota who studies the molecular mechanics of fundamental cellular processes, such as cell division and cell migration. Trained as a chemical engineer, Odde joined the newly created Department of Biomedical Engineering at the University of Minnesota in 1999 where he is a professor and Associate Director of the Institute for Engineering in Medicine. In his research, Odde's group builds computer models of cellular and molecular self-assembly and force-generation-dissipation dynamics, and tests the models experimentally using digital microscopic imaging of living cells ex vivo and in engineered microenvironments. Current applications include modeling the molecular mechanisms of neurodegeneration and of cancer cell migration through complex mechanical environments such as the brain. His group seeks to bring an engineering approach that uses physics-based modeling and analysis to understand, predict, and control disease outcomes (oddelab.umn.edu). Dr. Odde is an elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the Biomedical Engineering Society (BMES), and the American Association for the Advancement of Science (AAAS) and is the Director of the Physical Sciences in Oncology Center at the University of Minnesota (psoc.umn.edu), which is focused on modeling the mechanics of cancer cell migration in biologically relevant contexts.