Mechanics of Brain Cancer Cell Migration

Glioblastoma (GBM) is a highly malignant brain cancer with a median survival of 15 months and a 5-year survival rate of less than 5%. GBM is currently incurable due to the high proliferation and migration rates associated with tumors cells, which allow them to invade healthy tissue and evade current therapies. In this seminar, I will describe how we have developed a computational model for the biophysics of cell migration and applied it to glioma cell migration. Whereas an extensive literature across a wide range of cell types demonstrates the phenomenon of durotaxis – the tendency of cells to migrate toward mechanically stiffer environments – we demonstrate that our motor-clutch cell migration model (Bangasser et al., Nat Comm, 2017) predicts “negative durotaxis” – biasedmigration toward softer environments – which we confirm experimentally for the first time. Also, we used the model to mechanically phenotype genetically inducedglioma mouse models, in immune-competent mice, resembling human proneural and mesenchymal GBM subtypes. The biophysical modeling and experiments help point us toward potentially new therapeutic strategies.

 

Short Bio:

David Odde is a Medtronic Professor of Engineering in Medicine at the University of Minnesota. Trained as a chemical engineer at the University of Minnesota and Rutgers University, Odde joined the newly created Department of Biomedical Engineering at the University ofMinnesota in 1999 where he is a professor and Associate Director for StrategicResearch Initiatives in 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 andBiological Engineering (AIMBE), the Biomedical Engineering Society (BMES), theInternational Academy of Medical and Biological Engineering (IAMBE), and theAmerican 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. 

https://www.cancer.umn.edu/bio/btp-executive-members/david-odde

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