A single cell nanobiosensor for probing collective cell migration
Collective cell migration is a fundamental multicellular activity that plays essential roles in numerous physiological and pathological processes, such as angiogenesis, tissue regeneration, and cancer metastasis. Proper coordination of cells, for instance, is required to repair damaged tissues in which cells crawl collectively atop exposed extracellular matrix following injury. The collective migration mechanisms responsible for tissue development are also utilized in the invasion and metastasis of malignant tumors. Despite its importance, the fundamental processes that drive collective cell migration, such as leader cell formation and biomechanical coupling, remain poorly understood. To elucidate the collective migration process, my laboratory is developing molecular and nanoengineering techniques for single molecule imaging, dynamic gene expression analysis, single cell photothermal ablation, biomechanical analysis of cell-cell and cell-matrix interaction, and agent-based computational modeling. In this talk, I will discuss the application of a single cell nanobiosensor for probing the mechanoregulation of collective cell migration. The biosensor incorporates nanoparticles and fluorophore-labeled locked nucleic acid probes for mapping the spatiotemporal gene expression dynamics in native tissue microenvironments at the single cell level. Using the nanobiosensor, we demonstrate that the formation of leader cells during collective migration is dynamically regulated by Dll4 signaling through both Notch1 and mechanical force. Our finding provides a molecular basis for the stochastic emergence of leader cells, which may enable novel approaches in regenerative medicine, diabetic wound healing and cancer treatment.
Pak Kin Wong is a Professor of Biomedical Engineering, Mechanical Engineering and Surgery at the Pennsylvania State University. Prior to Penn State, Dr. Wong was an Associate Professor in the Departments of Aerospace and Mechanical Engineering and Biomedical Engineering and a member of the Southwest Environmental Health Sciences Center at the University of Arizona. He received his Ph.D. from the University of California, Los Angeles in 2005. He is an editor of Scientific Reports, IEEE Transaction on Nanotechnology IEEE Nanotechnology Magazine, and Journal of Laboratory Automation. He serves in organizing committees of numerous international conferences, including program chair of IEEE NANOMED 2012 and general co-chair of IEEE NEMS 2013. His current research interest focuses on collective cell migration and molecular diagnostics. He has published over 80 peer-reviewed journal articles in the area of nanotechnology and biomedical engineering, and is an inventor of two patents. Among other honors, Dr. Wong was awarded the NIH Director's New Innovator Award in 2010, Arizona Engineering Faculty Fellow in 2011, AAFSAA outstanding Faculty Award in 2013, and JALA 10 – A Top 10 Breakthrough in Innovation in 2015.
Molecular Engineering and Sciences Seminar Series
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.