January 31, 2003
Tuesday - 4:00 pm in Swain East 140
Speaker: Dr. Karen A. Beningo, University of Massachusetts Medical School, Worcester
Title: The Influence of Mechano-Chemical Interactions on Cellular Behavior
Abstract:
Mechano-chemical interactions between mammalian cells and the surrounding environment play an essential role in driving and regulating such important events as migration and phagocytosis. These interactions involve forces that are transmitted both from the cell to its surroundings (inside-out) and from the environment to the cell (outside-in). The forces in turn interface with signal transduction cascades that modulate a wide spectrum of cellular structures and enzymatic reactions. Elastic substrata composed of polyacrylamide embedded with fluorescent microbeads provide an effective means to study mechanical forces at this interface. Using this technique I discovered that small, newly formed adhesions at the leading edge of a migrating cell generate the strongest propulsive forces for migration. In addition, I found that the protease calpain, which targets components of the adhesion complex, plays a role in coordinating the adhesion and contractile events of migration. I have also probed how cells sense changes in their mechanical environment (outside-in), by challenging them with pulling forces, and with substrates or particles of different flexibility. Surprisingly, macrophages show a strong preference towards ingesting stiff particles. Finally, I have found that the spatial arrangement of mechano-chemical interactions have a profound effect on cellular behavior. Sandwiching cells between two polyacrylamide substrata demonstrate this fact. Cells in this more physiologically relevant environment display dramatic changes in cytoskeletal and adhesion organization leading to altered morphology and consequently a different mode of migration. Thus, a deeper understanding of mechano-chemical interactions between the cell and its environment has broad implications to many biological events including wound healing, embryonic development, immunological responses and cancer metastasis.