BME Seminar Series: Delphine Gourdon, Ph.D.
Thursday, March 12, 2015
Goergen Hall 101 (Sloan Auditorium)
"Altered Mechanobiology of the Extracellular Matrix Facilitates Tumor Growth and Metastasis"
Delphine Gourdon, Ph.D.
Department of Materials Science and Engineering
Graduate Field Member of Biomedical Engineering
Abstract: The extracellular matrix (ECM), a complex network of proteins including fibronectin (Fn) and collagen (Col), couples a cell with its microenvironment and directly regulates cell’s fate via mechanobiological cues. Therefore, any alteration to the ECM mechanobiology directly affects ECM signaling to surrounding cells. Understanding how these alterations occur and amplify over time in the context of breast cancer is essential to elucidating tumor growth and metastasis.
My lab has focused on (i) investigating the conformational, topological, and mechanical properties of both Fn and Fn-Col matrices by integrating fluorescence resonance energy transfer (FRET) with the Surface Forces Apparatus (SFA), and (ii) understanding how these ECM mechanobiological properties further affect cellular behavior, in particular cell adhesion, proliferation, and pro-angiogenic secretion. In a first example, I will show how this integrated method has allowed us to quantify early unfolding and stiffening of the ECM generated by pre-adipocyte cells in presence of tumor soluble factors, which in turn facilitate tumor vascularization and growth by increasing cell secretion of vascular growth factor VEGF. In a second example, I will present a model system we developed to mimic the interface between the ECM and bone (where breast cancer preferentially metastasizes) containing Fn and hydroxyapatite nanoparticles. Using this simple model system, I will show that hydroxyapatite materials properties (size, shape, crystallinity) control ECM deposition and conformation at the mineral/protein interface, which likely plays a role in cancer cell recruitment and metastasis. Collectively, these findings not only have important implications for our understanding of tumor growth and metastasis but also enhance our knowledge of cell-ECM mechanobiological interactions that may be harnessed for applications including biomaterials science and advanced tissue engineering approaches.