Samuel B. Eckert Professor in Engineering; Professor of Applied Physics
252 Clark Hall, (607) 255-3331,
B.S. 1947, Sc.D. 1955 (Massachusetts Institute of Technology)
Watt W. Webb is a Professor of Applied Physics and the S.B. Eckert Professor in Engineering. He joined the Cornell faculty in 1961 as Associate Professor of Engineering Physics and was named Professor of Applied Physics in 1965 and S.B. Eckert Professor in Engineering in 1998. He served as the Director of Cornell's School of Applied and Engineering Physics from 1983 to 1988. He began his career at Union Carbide Research Laboratories as a Research Engineer in 1947-1952. After receiving his Ph.D. in 1955, he returned to Union Carbide in successive positions as a Research Scientist (1955-1959), Coordinator of Fundamental Research (1959-1960), and Assistant Director of Research (1960-1961). As a Cornell faculty member, he has supervised over 60 Ph.D. theses.
Webb's recent awards include the National Lectureship of the Biophysical Society (2002), Rank Prize in Opto-electronics (2000), the Jablonski Prize of the Biophysical Society (2000), the Michelson-Morley Award of Case-Western Reserve University (1999), and the Biological Physics Prize of the American Physical Society (1991). He is an elected Fellow of the American Physical Society, the Biophysical Society, the American Association for the Advancement of Science, and Founding Fellow of the American Institute of Biological and Medical Engineers. He is an elected member of the National Academy of Engineering, the National Academy of Science, and the American Academy of Arts and Science. He lectures broadly and is active as a consultant and advisor.
Research Group website.
Research Interests
The solution of seeming impossible experimental problems drives our creation of new experimental technologies, which during the past thirty years have focused primarily on observing the dynamics of the biomolecular processes of life. This challenge requires benign, effectively non-invasive methods that frequently push the physical limits of resolution in space, time and sensitivity. The first of them we invented is Fluorescence Correlation Spectroscopy to observe the dynamics of molecular binding of regulatory proteins to DNA. Most recently, we have extended these methods to observations of gene transduction in vivo.
Seeming Impossible Biological Problems
Several of these innovations: Multiphoton Microscopy (MPM), Fluorescence Correlation Spectroscopy (FCS), nanoscopic molecular tracking and most recently, nanostructured molecular dynamic probes are being applied to some of these seeming impossible biological problems. Over the years, about 35 of our publications have focused on the challenges of neuroscience, including: molecular mechanisms and physics of auditory transduction, the first successful single channel recording of reconstituted natural ion channels and on their structural fluctuations and mechano-sensitivity, signal delays along neural processes in neural networks, detection and imaging of serotonin and its secretion, imaging the development of the lesions of Alzheimer’s Disease in transgenic mice, and recently successful optical imaging of the propagation of action potentials along in live neural networks.
Clinical Medicine
As our biophysical research has evolved, we have come closer to realizing direct applications of our techniques in clinical medicine. Thus, our current multiphoton imaging research focuses on in vivo imaging, particularly on disease states generated in transgenic animal models of human diseases and on development of potential medical tools such as Medical Multiphoton Microscopic-Endoscopy (M-MPM-E) for successful optical diagnostics, now demonstrated in urological cancer. This strategy now impinges on the realm of biomedical engineering.
Membrane Heterogeneity
Our early emphasis on optical measurement of molecular mobility in cell membranes led to the engineering of Fluorescence Photobleaching Recovery, also called FRAP and later to the first nanoscopic tracking of the individual cell surface receptor molecules in the complete population on living cells, which led eventually to evidence for the membrane heterogeneity now known as "membrane rafts" in the form of our discovery of anomalous subdiffusion and diversity of characteristics of tracking trajectories on the living cell surfaces. We have recently resumed research on the fundamentals of membrane heterogeneity, motivated by the chronic violations of the elementary paradigms of chemical physics in its current biological discussions. We have recently analyzed the behavior of large multiphase bilayer vesicles to measure the interphase energies (line tension) for the first time, detect the effects of the Gaussian curvature energy of membranes and discover the facilitation of vesicle budding by interphase tensions. This research also demonstrated the onset of critical fluctuations in these two-dimensional fluids as the temperature approached the line of critical points where the two phases merge and the energy cost of fluctuations and the interphase tension vanish. It is ironical that the three-dimensional analog of precisely this problem was first observed and studied in our laboratory nearly 40 years ago.
Enzyme Kinetics
We have also recently developed methods for detection and measurements of enzyme kinetics with single molecule sensitivity to measure enzyme kinetics fluctuations, individual particle detection sensitivity and molecular size scaling even to attomolar concentrations, and convenient small volume chemical kinetics with fast enough mixing for one microsecond time resolution (presently we reach about 30 microseconds).
Research Grants
Webb's recent awards include the National Lectureship of the Biophysical Society (2002), Rank Prize in Opto-electronics (2000), the Jablonski Prize of the Biophysical Society (2000), the Michelson-Morley Award of Case-Western Reserve University (1999), and the Biological Physics Prize of the American Physical Society (1991). He is an elected Fellow of the American Physical Society, the Biophysical Society, the American Association for the Advancement of Science, and Founding Fellow of the American Institute of Biological and Medical Engineers. He is an elected member of the National Academy of Engineering, the National Academy of Science, and the American Academy of Arts and Science. He lectures broadly and is active as a consultant and advisor.
Research Group website.
Research Interests
The solution of seeming impossible experimental problems drives our creation of new experimental technologies, which during the past thirty years have focused primarily on observing the dynamics of the biomolecular processes of life. This challenge requires benign, effectively non-invasive methods that frequently push the physical limits of resolution in space, time and sensitivity. The first of them we invented is Fluorescence Correlation Spectroscopy to observe the dynamics of molecular binding of regulatory proteins to DNA. Most recently, we have extended these methods to observations of gene transduction in vivo.
Seeming Impossible Biological Problems
Several of these innovations: Multiphoton Microscopy (MPM), Fluorescence Correlation Spectroscopy (FCS), nanoscopic molecular tracking and most recently, nanostructured molecular dynamic probes are being applied to some of these seeming impossible biological problems. Over the years, about 35 of our publications have focused on the challenges of neuroscience, including: molecular mechanisms and physics of auditory transduction, the first successful single channel recording of reconstituted natural ion channels and on their structural fluctuations and mechano-sensitivity, signal delays along neural processes in neural networks, detection and imaging of serotonin and its secretion, imaging the development of the lesions of Alzheimer’s Disease in transgenic mice, and recently successful optical imaging of the propagation of action potentials along in live neural networks.
Clinical Medicine
As our biophysical research has evolved, we have come closer to realizing direct applications of our techniques in clinical medicine. Thus, our current multiphoton imaging research focuses on in vivo imaging, particularly on disease states generated in transgenic animal models of human diseases and on development of potential medical tools such as Medical Multiphoton Microscopic-Endoscopy (M-MPM-E) for successful optical diagnostics, now demonstrated in urological cancer. This strategy now impinges on the realm of biomedical engineering.
Membrane Heterogeneity
Our early emphasis on optical measurement of molecular mobility in cell membranes led to the engineering of Fluorescence Photobleaching Recovery, also called FRAP and later to the first nanoscopic tracking of the individual cell surface receptor molecules in the complete population on living cells, which led eventually to evidence for the membrane heterogeneity now known as "membrane rafts" in the form of our discovery of anomalous subdiffusion and diversity of characteristics of tracking trajectories on the living cell surfaces. We have recently resumed research on the fundamentals of membrane heterogeneity, motivated by the chronic violations of the elementary paradigms of chemical physics in its current biological discussions. We have recently analyzed the behavior of large multiphase bilayer vesicles to measure the interphase energies (line tension) for the first time, detect the effects of the Gaussian curvature energy of membranes and discover the facilitation of vesicle budding by interphase tensions. This research also demonstrated the onset of critical fluctuations in these two-dimensional fluids as the temperature approached the line of critical points where the two phases merge and the energy cost of fluctuations and the interphase tension vanish. It is ironical that the three-dimensional analog of precisely this problem was first observed and studied in our laboratory nearly 40 years ago.
Enzyme Kinetics
We have also recently developed methods for detection and measurements of enzyme kinetics with single molecule sensitivity to measure enzyme kinetics fluctuations, individual particle detection sensitivity and molecular size scaling even to attomolar concentrations, and convenient small volume chemical kinetics with fast enough mixing for one microsecond time resolution (presently we reach about 30 microseconds).
Research Grants
- NIH-NIBIB, Development of Medical Multiphoton Microscopy Endoscopy
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NIH-NIA, Nascent Dynamic Intermediates in Amyloid Aggregation
- NSF, Regulatory Protein-DNA Interactions in vivo Analyzed by Ultrafast Photochemical Crosslinking
- Kwan, A.C., Duff, K., Gouras, G.K., and Webb, W.W., “Optical visualization of Alzheimer’s pathology via multiphoton-excited intrinsic fluorescence and second harmonic generation” Optics Express 17(5), 3679-3689, 2009
- Xu, H., Zhu, P., Craighead, H.G., and Webb, W.W., “Resonantly enhanced transmission of light through subwavelength apertures with dielectric filling” Optics Communications 282, 1467-1471, 2009
- Chen, H. E. Rhoades, J.S. Butler, S.N. Loh and W.W. Webb, “Dynamics of Equilibrium Folding Fluctuations of Apomyoglobin Measured by Fluorescence Correlation Spectroscopy,” PNAS 104(25), 10459-10464, 2007
- Yao, J., K. Munson, W. W. Webb and J. T. Lis, "Dynamics of Heat Shock Factor Association with Native Gene Loci in Living Cells," Nature 442(7106), 1050-1053, 2006
- Williams, R.M., W.R. Zipfel, and W.W. Webb, “Interpreting Second Harmonic Generation Images of Collagen I Fibrils,” Biophysical Journal 88, 1377-1386, 2005
- Kasischke, K. A., H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305(5680), 99-103, 2004
- Levene, M. J., J. Korlach, S. W. Turner, M. Foquet, H. G. Craighead and W. W. Webb, "Zero-mode waveguides for single molecule analysis at high fluorophore concentrations," Science 299, 682-686, 2003
- Zipfel, W. R., R. M. Williams and W. W. Webb, “Nonlinear Magic: Multiphoton Microscopy in the Biosciences,” Nature Biotechnology 21(11), 1369-1377, 2003
- Christie, R.H., B.J. Bacskai, W.R. Zipfel, R.M. Williams, S.T. Kajdasz, W.W. Webb and B.T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimer's disease observed by in vivo multiphoton microscopy," Journal of Neuroscience 21(3), 858-864, 2001
- Webb, W.W., "Fluorescence Correlation Spectroscopy: Inception, biophysical experimentations and prospectus," Applied Optics 40(24), 3969-3983, 2001
- Christie, R.H., B.J. Bacskai, W.R. Zipfel, R.M. Williams, S.T. Kajdasz, W.W. Webb and B.T. Hyman, "Growth arrest of individual senile plaques in a model of Alzheimerýs disease observed by in vivo multiphoton microscopy," Journal of Neuroscience 21(3), 858-864, 2001
- Schwille, P., U. Haupts, S. Maiti and W.W. Webb, "Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation," Biophys. J. 77(4), 2251-2265, 1999
- Xu, C. and W. W. Webb, "Measurement of two-photon excitation cross sections of molecular fluorophores with data from 690 to 1050 nm," JOSA B-Optical Physics 13(3), 481-491, 1996
- Denk, W., J.H. Strickler and W.W. Webb, “Two-Photon Laser Scanning Fluorescence Microscopy,” Science 248 (4951), 73-76, 1990
- Ryan, T.A., J. Myers, D. Holowka, B. Baird and W.W. Webb, "Molecular Crowding On the Cell-Surface," Science 239(4835), 61-64, 1988
- Wack, D.C. and W.W. Webb, "Measurements of Modulated Lamellar P-Betaý Phases of Interacting Lipid-Membranes," Phys. Rev. Lett. 61(10), 1210-1213, 1988
- Tank, D.W., R.L. Huganir, P. Greengard and W.W. Webb, "Patch-Recorded Single-Channel Currents of the Purified and Reconstituted Torpedo Acetylcholine-Receptor," PNAS 80(16), 5129-5133, 1983
- Barak, L.S. and W.W. Webb, "Diffusion of Low-Density Lipoprotein-Receptor Complex On Human- Fibroblasts," J. Cell Biol. 95(3), 846-852, 1982
- Magde, D., W.W. Webb and E. Elson, "Thermodynamic Fluctuations in a Reacting System - Measurement by Fluorescence Correlation Spectroscopy," Phys. Rev. Lett. 29(11), 705-708, 1972
- Beasley, M. R., R. Labusch and W. W. Webb, "Flux Creep in Type-2 Superconductors," Physical Review 181(2), 682, 1969
Full Publication List
