Principal Investigator C Dewey
The primary medical problem that the Dewey research group investigates is atherosclerosis. The lumen of the arterial wall is lined with endothelial cells that respond to the mechanical forces of blood flowing through the arteries and protect the artery wall from inflammatory reactions that result in atherosclerosis. Our lab was the first to demonstrate the time-course with which endothelial cell reorganize and reorient in the direction of fluid flow, and we continue to use microscopy to probe the fundamental mechanisms of this response. The mechanical structure of vascular endothelial cells depends on a network of polymerized actin, and we use fluorescent dyes to track individual actin molecules as they diffuse through the cell. In our in vitro model system, application of fluid shear force that is comparable to vascular blood flow in vivo induces a major transient decrease in polymerization. We believe that this alteration is correlated with the observed realignment of the cells in the flow direction. Measurements of cell motility and intercellular gap junction proteins are extending our understanding of the interaction process.
As part of this project, we are collaborating with colleagues at the University of Rochester to develop a computation model of actin polymerization. The ability to peer inside individual cells with modern fluorescence techniques has powered a profound change in our quantitative understanding of cellular biological function. For example, we reconstruct 3-dimensional images from stereo image pairs taken with a scanning electron microscopy (SEM). These images allow us to see the interaction of individual structural features within the cells at the molecular level, e.g, interactions between polymerized actin filaments and the actin binding protein filamin-A.