Purdue University School of Chemical Engineering Graduate Seminar Series Dr. Denis Wirtz Theophilus H. Smoot Professor Department of Chemical & Biomolecular Engineering and Physical Sciences in Oncology Center John Hopkins University “Cancer Cell Motility in 3D” December 7, 2010 3:30 - 4:30 p.m. FRNY G140 Abstract: Focal adhesions are large multi-protein clustered assemblies that form at the basal surface of cells placed on planar dishes which mediate cell signaling, force transduction, and adhesion with the underlying substratum. While much is known about the organization and function of focal adhesion components in 2-D systems, their organization and function in migrating cells within a more physiological three-dimensional (3-D) matrix is largely unknown. Quantitative live-cell microscopy shows that for cells fully embedded in a 3-D matrix focal adhesion proteins, including vinculin, paxillin, talin, -actinin, zyxin, VASP, FAK, and p130Cas, do not cluster into appreciable aggregates, but are diffusively distributed in the cytoplasm of cells. Despite the absence of detectable focal adhesions, focal adhesion proteins still modulate cell motility but in a manner distinct from cells moving on conventional planar substrates. Rather, focal adhesion proteins in matrix-embedded cells regulate cell speed by affecting protrusion activity and matrix deformation, two processes that play no direct role in controlling 2-D cell speed. This study shows that actively growing membrane protrusions constitute a critical motility/matrix-traction module that drives cell motility in a 3-D matrix. We will discuss the implications of this work in cancer metastasis. Bio: Denis Wirtz is Theophilius H. Smoot Professor of Engineering Science and Oncology at Johns Hopkins University. He is co-Director of the Johns Hopkins Institute for NanoaBioTechnology (INBT), Director of the Howard Hughes Medical Institute-funded graduate training program in nanotechnology for biology and Medicine, Director of the NCI-funded postdoctoral and predoctoral training programs in nanotechnology for cancer medicine, and Director of the new NCI-funded Physical Sciences in Oncology Center. Dr. Wirtz has made contributions in molecular and biophysical mechanisms of cell motility and adhesion and nuclear dynamics in health and disease. Dr. Wirtz earned his Engineering Physics degree at the Université Libre de Bruxelles in Belgium and M.Sc. and PhD in Chemical Engineering at Stanford University. Dr. Wirtz is a fellow of the AAAS and the AIMBE.