William Guilford William Guilford

Associate Professor of Biomedical Engineering
Undergraduate Program Director


B. S., Saint Francis College, 1986
Ph.D., Physiology, University of Arizona, 1993

Box 800759
University of Virginia
Charlottesville, VA 22908

Office: Room 1111 Phone: 434-243-2740
Lab: Room 1213 Phone: 434-924-9908

whg2n@virginia.edu

CV

   

Research Interests

movieIn the Molecular Biomechanics Laboratory, our goal is to understand the molecular mechanisms by which cells move, with particular emphasis on muscle contraction. We examine the mechanics of these processes at the level of individual molecules using a laser trap as an important experimental tool. A laser trap is, quite literally, a "tractor beam" of Star Trek fame that works at a microscopic scale. With a laser trap, small translucent particles can be captured 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. Our powerful combination of the laser trap with other biochemical and imaging techniques allows us to study the force and motion generated by molecular motors, and the strength of single ligand-receptor bonds. Together, these molecules define the molecular underpinnings of many cell movements, and the molecular basis of many diseases.

We are currently studying several fundamental issues in cell movement. First, we are studying the role of the protein tropomyosin in the regulation of muscle contraction. Phosphorylation of this protein may have previously unknown effects on muscle contraction. Using the motility assay - reconstituted muscle contraction using purified proteins (pictured) - and measurements of single intermolecular bond mechanics, we are finding that tropomyosin contributes to muscle mechanics in an unexpected, phosphorylation-dependent manner.

Second, in collaboration with Dr. Lawrence we are measuring the mechanics and kinetics of individual selectin adhesion bonds, important in leukocyte trafficking, inflammation, and the development of atherosclerosis. The bonds between selectins and their ligands strengthen as load is applied, akin to a "finger trap." The load-dependent kinetics of these molecules are critical to their function in the body - mediating bonds between white cells and endothelial cells under flow.

Finally, we are doing first of their kind studies on the mechanics of individual molecular motors driving intracellular transport of cargo. Molecular motors move organelles and other cargo bidirectionally across the cell, and how oppositely-directed motors work together and are controlled is of tremendous interest to cell biologists. We developed a novel experimental platform combining the laser trap with the unicellular alga Chlamydomonas that allows us to study the biomechanics and coordination of molecular motors inside the living cell from outside the cell.

Recent Publications

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