Invited external talk at the Glasgow Biomaterials Seminar Series
October 15th 2015
Prof. Delphine Gourdon
Cornell University, NY, USA
Abstract by Delphine Gourdon:
The extracellular matrix (ECM), a complex network of proteins including collagen (COL) and fibronectin (FN) couples a cell with its environment and directly regulates the cell’s fate via physical and biochemical signals. Although the ECM was often considered a static structure providing cohesion and mechanical integrity to tissues, it has recently been shown that (i) the nano-structure, (ii) the nano/micro mechanics, and (iii) the signaling capacity of the ECM are affected by cell-generated forces. Our work has focused on investigating and controlling the material properties of ECM networks and the synergistic roles of FN and COL in 2D and 3D environments.In a first example, I will show how the integrated method used in our lab allowed us to diagnose early dysregulation of the ECM materials properties in tumors. In a second example, I will present a 3D conducting matrix-mimicking polymeric platform we developed to control FN conformation over macroscopic volumes. This platform enables a better understanding of the critical link between protein structure and function, with the ultimate goal of controlling cellular functions through cell-matrix interactions. As such, it represents a new tool for biological research with many potential applications in basic research, medical diagnostics, and tissue engineering.
More about Delphine's research: https://sites.google.com/site/gourdongroup/
Papers mentioned in the talk:
Wang K., Seo B.R., Fischbach C. and Gourdon D. Fibronectin Mechanobiology Regulates Tumorigenesis (Review article). Published online in Cellular and Molecular Bioengineering (August 2015) DOI: 10.1007/s12195-015-0417-4 (open).
B.R. Seo, J. Gonzalez, P. Bhardwaj, R.A. Eguiluz, K. Wang, H. Sha, S. Mohanan, R.M. Williams, L.T. Vahdat, L. Qi, O. Reizes, A. J. Dannenberg, D. Gourdon and C. Fischbach. Obesity-dependent changes of interstitial ECM mechanics and their role in breast tumorigenesis. Science Translational Medicine 7, 301ra130 (2015). Published online on August 19, 2015. DOI: 10.1126/scitranslmed.3010467. Associated Science AAAS News, DOI:10.1126/science.aad1648 (open).
Kubow K., Vukmirovic R., Klotzsch E., Smith M., Gourdon D., Luna S. and Vogel V. Mechanical Forces Regulate the Interactions of Fibronectin and Collagen I in Extracellular Matrix. Nature Communications 6, 8026 (2015). DOI: 10.1038/ncomms9026 (open).
A.M.D. Wan, S. Inal, T. Williams, K. Wang, P. Leleux, L. Estevez, E.P. Giannelis, C. Fischbach, G.G. Malliaras, and D. Gourdon. 3D conducting polymer platforms for electrical control of protein conformation and cellular functions. J. Mater. Chem. B 3, 5040–5048 (2015). DOI: 10.1039/C5TB00390C.
Wang K., Eguiluz R.A., Wu F, Seo B.R., Fischbach C. and Gourdon D. Stiffening and unfolding of early deposited-fibronectin activate proangiogenic secretion by breast cancer-associated stromal cells. Biomaterials 54, 63–71 (2015). DOI: 10.1016/j.biomaterials.2015.03.019 (open).
Wan, A. M. D., Schur, R. M., Ober, C. K., Fischbach, C., Gourdon, D. and Malliaras, G. G. Electrical Control of Protein Conformation. Adv. Mater. 24, 2501–2505 (2012). DOI: 10.1002/adma.201200436.
E.M. Chandler, M.P. Saunders, C.J. Yoon, D. Gourdon, and C. Fischbach. Adipose progenitor cells increase fibronectin matrix strain and unfolding in breast tumors. Phys. Biol. 8(1), 015008 (2011). DOI: 10.1088/1478-3975/8/1/015008.
E. Klotzsch, M. Smith, K. Kubow, S. Muntwyler, W. Little, F. Beyeler, D. Gourdon, B. Nelson and V. Vogel. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. Proc. Natl. Acad. Sci. USA 106, 18267 (2009). DOI: 10.1073/pnas.09075181106 (open).
M.L. Smith, D. Gourdon, W. Little, K.E. Kubow, R. Andresen Eguiluz, S. Luna-Morris and V. Vogel. Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biology 5, e268 (2007). DOI: 10.1371/journal.pbio.0050268 (open).
J. Israelachvili and D. Gourdon. Putting liquids under molecular-scale confinement. Science 292, 867 (2001). DOI: 10.1126/science.1061206.
Seo, B. R., Bhardwaj, P., Choi, S., Gonzalez, J., Andresen Eguiluz, R. C., Wang, K., … Fischbach, C. (2015). Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis. Science Translational Medicine, 7(301), 301ra130–301ra130. Retrieved from http://stm.sciencemag.org/content/7/301/301ra130.abstract