January 18, 2002
Colloquium Speaker: Scot Kuo
Dr. Scott C. Kuo received his Ph.D. from University of California at Berkeley and his B.A., magna cum laude with Highest Honors in Biochemistry from Harvard University. After Post-Doctoral Fellowships at Washington University and Duke University, he joined the Johns Hopkins University School of Medicine in 1993 and is currently Associate Professor of Biomedical Engineering. Dr. Kuo has been a leader in laser-based optics applied to cell biology and cell mechanics. While studying the molecular motor kinesin, he was the first to measure molecular forces using optical tweezers. Expanding the capabilities of optical approaches, his current laser-tracking instrumentation allows real-time measurements of cellular processes, including eating and crawling. His current research applications are studying the cell-to-cell spreading of the bacterial pathogen, Listeria monocytogenes, as it hijacks the actin-based machinery that cells normally use for crawling. In 2001, Dr. Kuo received the Robert S. Pond, Sr. Excellence in Teaching Award of the Whiting School of Engineering.
When cells crawl and eat, they regulate the structure of biological polymers to exert forces on their environment. These changes in cell mechanics can be very fast and demand new technology to characterize cell behavior. By high-resolution laser-tracking, we can measure the subnanometer motions of individual particles and reveal the biophysics of cell motility. I will describe two applications of this developing technology. 1) By tracking the Brownian motions of tracer particles, laser-tracking micro-rheology (LTM) can accurately quantify moduli of polymeric solutions. In measurements ~ls in duration, LTM can determine if materials are liquid-like or solid-like at various time-scales. LTM is ideal for cells, and real-time measurements will be presented. 2) For biochemical understanding, we study the actin-based motility of the intracellular pathogen, Listeria monocytogenes, which hijacks the machinery that cells normally use for crawling and eating. Laser-tracking shows that Listeria unexpectedly move with extremely small steps (~5.4nm, which is the spatial periodicity of F-actin). Biophysical models, such as the Brownian ratchet, are disproved and must be modified. Despite the extremely high forces of actin-based motility, LTM also generated its first load-velocity measurements. For Listeria, the force-velocity relationship is unusually biphasic and indicate a self-strengthening mechanism for motility. Although uses of laser-based nano-tracking are still developing, it has a clear niche for measuring cell mechanics.