Kenneth Jacobson, Ph.D., Professor, SUNY at Buffalo, 1972

Dr. Jacobson teaches in The Cell and Medical Cell Biology, as well as in the Imaging Course for the Carolina Workshop. He is on the Editorial Boards of the Biophysical Journal and Cell Motility and the Cytoskeleton, and he serves on the Advisory Boards for the Center for Fluorescence Dynamics, Univ. of Ill; the Virtual Cell Computer Modeling Resource at the University of Connecticut, Univ. of Wisc.; and the Solar Development Initiative of the North Carolina Solar Center. Dr. Jacobson is also the Associate Director of the Department of Cell Biology and Anatomy's Cell and Molecular Imaging Facility.

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Research Interests

Our laboratory is interested in the fundamental microstructure of membranes, what factors determine the lateral mobility of membrane proteins and lipids, and how such mobility is related to the functions that membranes carry out. To investigate this problem we use a combination of video microscopic, laser trapping and molecular cell biology techniques. By tracking the individual movements of single lipids tagged with 30 nm gold particles, we have found that the two-dimensional Brownian motion of lipids in the plane of the membrane can be directly observed by video microscopy. This new technology, as applied to membrane proteins, promises to reveal subtle features of the lateral organization and dynamics of individual membrane proteins. For example, GPI-anchored proteins and glycolipids are found to be transiently confined to small (about 300 nm) zones. Such zones may represent lipid rafts - structures that could be hot spots for signal transduction at the plasma membrane. We are currently attempting to further characterize the physical and chemical properties of these "transient confinement zones" and to reconstitute "rafts" in model bilayer membranes. A future question will be how cell interactions with environmental cues alter the local and global structure of the plasma membrane; the answer will have basic relevance to developmental and cancer biology.

Our laboratory is also interested in the problem of how cells move; this research is relevant to the aberrant cell motility exhibited in metastasis and to transendothelial cell migration involved in aspects of the inflammatory response. The intellectual challenge is to relate global descriptions of cell movement and force production to molecular mechanisms. We have completed a kinematic description accounting for how locomoting fish scale keratocytes maintain constant shape and speed. This model accounts for not only dynamic morphological behavior but also the behavior of the cytoskeletal meshwork and cell surface receptors. We have also developed the first quantitative assay for the strength and pattern of the traction forces exerted by moving cells and shown how the traction pattern exhibited by keratocytes can be explained. We have recently studied the adhesive contacts the motile cell makes to the substratum and how intracellular calcium is involved in traction force production by regulating cell contractility and/or adhesion. Ongoing work involves locally perturbing cell locomotion using single cell photomanipulative techniques including chromophore assisted laser inactivation [CALI] to knock out molecules responsible for cell adhesion and photoactivation to quickly increase the concentration of proteins that regulate the actin cytoskeleton. These data will be used to check the predictive power of quantitative models of cell locomotion developed by our theoretical collaborators.

Please visit the Jacobson lab web site.

PUBLICATIONS:

Jacobson, K., Sheets, E.D. and Simson, R. "Revisiting the Fluid Mosaic Model of Membranes", Science, 268:1441-1442 (1995).

Dietrich et al., "Lipid rafts reconstituted in model membranes", Biophys. J., in press.

Lee, J., Ishihara, A., Oxford, G. and Jacobson, K. "Regulation of cell movement is mediated by stretch-activated calcium channels", Nature, 400: 382-386 (1999).

Oliver, T., Dembo, M., and Jacobson, K. "Separation of propulsive and adhesive traction stresses in locomoting keratocytes", J. Cell Biol., 145: 589-604 (1999).

Lee, J., Ishihara, A., Theriot, J. and Jacobson, K. "Principles of Locomotion for Simple-Shaped Cells", Nature, 362: 167-171 (1993).