Cancer cell migration in 3D
Two-dimensional (2D) in vitro culture systems have for a number of years provided a controlled and versatile environment for mechanistic studies of cell adhesion, polarization, and migration, three interrelated cell functions critical to cancer metastasis. However, the organization and functions of focal adhesion proteins, protrusion machinery, and microtubule-based polarization in cells embedded in physiologically more relevant 3D extracellular matrices is qualitatively different from their organization and functions on conventional 2D planar substrates. This talk will describe the implications of the dependence of focal adhesion protein-based cell migration on micro-environmental dimensionality (1D vs. 2D vs.. 3D), how cell micromechanics plays a critical role in promoting local cell invasion, and associated validation in mouse models. We will also discuss the molecular and biophysical mechanisms used by cancer cells to negotiate different matrix microstructures. Finally, we will discuss the implications of this work in cancer metastasis.
Bio
Denis Wirtz is the Vice Provost for Research and Theophilus H. Smoot Professor of Chemical and Biomolecular Engineering in the Whiting School. Wirtz directs the Johns Hopkins Physical Sciences-Oncology Center and co-directs the Cancer Nanotechnology Training Center, both National Cancer Institute-funded entities. He also serves as associate director of the Johns Hopkins Institute for NanoBioTechnology.
Wirtz studies the biophysical properties of healthy and diseased cells, including interactions between adjacent cells and the role of cellular architecture on nuclear shape and gene expression. Cell biophysics, single molecule manipulation, intracellular particle trafficking, instrument development, tissue engineering, and nanotechnology in biology and medicine are among his research interests. Wirtz was elected Fellow of the American Association for the Advancement of Science for his contributions to cell micromechanics and cell adhesion. AAAS also recognized Wirtz for his development and applications for particle tracking methods to probe the micromechanical properties of living cells in normal conditions and disease state. In addition, Wirtz is a fellow of the American Physical Society and the American Institute for Medical and Biological Engineering. He is a past recipient of the National Science Foundation’s CAREER Award and the Whitaker Foundation Biomedical Engineering Foundation Award.
Wirtz earned his bachelor’s degree in Engineering Physics from the Université Libre de Bruxelles in Belgium and master’s and doctoral degrees in Chemical Engineering from Stanford University. He joined the Johns Hopkins faculty in 1994 and has joint appointments in the Department of Materials Science and Engineering at the Whiting School of Engineering, as well as the Departments of Oncology and Pathology at the Johns Hopkins School of Medicine.