University of Virginia Health System

In the Molecular Biomechanics Laboratory, our goal is to understand the molecular mechanisms by which cells move, with particular emphasis on muscle contraction, and how this relates to cardiovascular disease. We examine the mechanics of these processes at the level of individual molecules using techniques including the in vitro motility assay and laser trap transducer. The in vitro motility assay is a means by which the mechanics of the individual proteins that cause muscle contraction, actin and myosin, can be studied in isolation from other cell components. A laser trap is, quite literally, a "tractor beam" of Star Trek fame that works only at a microscopic scale. Single cells and small translucent particles can be trapped and held in three-dimensional space. The laser trap may also be used to measure the elasticity, distance moved, or force generated by single protein molecules. We are using the laser trap in combination with the motility assay to study the force and motion generated by myosin and the strength of single adhesion receptor bonds. Together, these molecules define the molecular underpinnings of many cell movements, and the molecular basis of many diseases. We are studying three fundamental issues in cell movement. First, to understand the molecular basis of myocardial damage following ischemia, we are collaborating with Dr. Brent French to study the mechanics of myosin exposed to the reactive ions nitric oxide and peroxynitrite. Second, we are studying the aggregate behavior of several myosin molecules working in parallel to determine if individual myosin heads cooperate in generating force and motion. Finally, in collaboration with Drs. Lawrence and Ley we are measuring the mechanics and kinetics of individual adhesion bonds, important in inflammation and the development of atherosclerosis.

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