Mechanical Modeling of Breast Cancer Metastasis

In general, I am interested in investigating the communication schemes that allows a large number of cells with limited computational ability can perform complex signal processing and react appropriately. I worked with Chris Rycroft, PhD at Harvard University, investigating the mechanisms by which breast cancer spreads through breast tissue and eventually metastasizes. An interesting phenomenon associated with this process is the formation of long collagen fibers in the tissue between the mammary acini normally responsible for milk production. This fiber formation then in turn causes breast cells to be structurally disorganized and forms the scaffolding for tumor growth. We hypothesized that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific physics of collagen. However, modeling such a system analytically and explicitly would result in hundreds of equations that would ultimately be intractable. To work around this limitation, I developed numerical methods to simulate a large number of cells growing in and influencing a physical extracellular matrix. The end product was a simulation engine to predict the behavior of a multicellular ensemble with respect to both cell-cell communication and cell-environment contact. Biologically, we also demonstrated that breast cancer was taking advantage of specific nonlinearities in collagen’s elastic behavior, in that collagen demonstrates more resistance to tension and pulling rather than compression, which led to this fiber formation.