Professor Axelrod’s group develops novel optical microscopy techniques to study the motion and organization of biological molecules and cellular organelles near biological surfaces. Many biological aspects are done in collaboration with research groups at the University of Michigan Medical School.

One of the projects examines the mechanisms of stimulated secretion of adrenaline-containing vesicles from chromaffin cells as studied mainly by time lapse total internal reflection (TIR) fluorescence quantitative imaging and analysis. The novel optical techniques allow us to study how vesicles that are secreted differ in their motions from vesicles that are not secreted. When cells are chemically stimulated, a large variety of responses ensue. Neutrophil cells are particularly interesting in this regard because they are involved in responding to infections. In collaboration with researchers in the U-M Biological Chemistry Department, we study (mainly by time lapse TIR fluorescence quantitative imaging and analysis) the calcium transients, actin assembly dynamics, and receptor binding kinetics in stimulated neutrophil cells. Dynamic Light Scattering (DLS) is a standard technique for measuring the diffusive rates of biological molecules. It is based on the interference-induced “twinkling” of laser light scattering from ensembles of moving molecules. We are developing a new spatially-resolved imaging approach to DLS such that it can be used in a microscope to view the rates of molecular motions in living cells.

Other optical biophysics techniques under development include detection of single biomolecules based on surface plasmon radiation, and fast new methods for detecting fluorescence resonance energy transfer in living cells among molecular neighbors that associate with each other only transiently.

Professor Axelrod is a Fellow of the Biophysical Society.

Restriction of Secretory Granule Motion Near the Plasma Membrane of Chromaffin Cells, (L.M. Johns, E.S. Levitan, E.A. Shelden, R.W. Holz, and D. Axelrod), J. Cell Biol. 153, 177-190 (2001).

Surface-Selective Fluorescence Imaging with a Very High Aperture Objective, (D. Axelrod), J. Biomed. Opt. 6, 6-13 (2001).

Total Internal Reflection Fluorescence Microscopy in Cell Biology, (D. Axelrod), Traffic 2, 764-774 (2001).

Actin Dynamics at the Living Cell Submembrane Imaged By Total Internal Reflection Fluorescence Photobleaching, (S.E. Sund and D. Axelrod), Biophys. J. 79, 1655-1669 (2000).

Cell Membrane Orientation Visualized By Polarized Total Internal Reflection Fluorescence, (S.E. Sund, J.A. Swanson, and D. Axelrod), Biophys. J. 77, 2266-2283 (1999).

Membrane Proximal Calcium Transients in Stimulated Neutrophils Seen By Total Internal Reflection Fluorescence, (G.M. Omann, and D. Axelrod), Biophys. J. 71, 2885-2891 (1996).