Our Faculty > William H. Guilford

William H. Guilford

William H. Guilford

Education

  • BS, Saint Francis College
  • PhD, University of Arizona
  • Postdoc, University of Vermont

Primary Appointment

  • Associate Professor, Biomedical Engineering

Contact

Research Interest(s)

Molecular Mechanics of Muscle Contraction in Cardiovascular Disease

Research Description



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.

http://www.bme.virginia.edu/people/faculty/guilford/

http://yakko.bme.virginia.edu/lab/

Selected Publications

  • Guilford W, Dupuis D, Kennedy G, Wu J, Patlak J, Warshaw D. Smooth muscle and skeletal muscle myosins produce similar unitary forces and displacements in the laser trap. Biophysical journal. 1997;72(3): 1006-21. PMID: 9138552 | PMCID: PMC1184489
  • Dupuis D, Guilford W, Wu J, Warshaw D. Actin filament mechanics in the laser trap. Journal of muscle research and cell motility. 1997;18(1): 17-30. PMID: 9147990
  • Guilford W, Warshaw D. The molecular mechanics of smooth muscle myosin. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 1998;119(3): 451-8. PMID: 9734329
  • Cheezum M, Walker W, Guilford W. Quantitative comparison of algorithms for tracking single fluorescent particles. Biophysical journal. 2001;81(4): 2378-88. PMID: 11566807 | PMCID: PMC1301708
  • Teaching peer review and the process of scientific writing. Advances in physiology education. 2002;25(1): 167-75. PMID: 11824193
  • Rinko L, Lawrence M, Guilford W. The molecular mechanics of P- and L-selectin lectin domains binding to PSGL-1. Biophysical journal. 2003;86(1): 544-54. PMID: 14695299 | PMCID: PMC1303823
  • Guo B, Guilford W. The tail of myosin reduces actin filament velocity in the in vitro motility assay. Cell motility and the cytoskeleton. 2004;59(4): 264-72. PMID: 15505809
  • Guilford W, Tournas J, Dascalu D, Watson D. Creating multiple time-shared laser traps with simultaneous displacement detection using digital signal processing hardware. Analytical biochemistry. 2004;326(2): 153-66. PMID: 15003556
  • "Shrink wrapping" lectures: teaching cell and molecular biology within the context of human pathologies. Cell biology education. 2005;4(2): 138-42. PMID: 15917872 | PMCID: PMC1103715
  • Guo B, Guilford W. Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle contraction. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(26): 9844-9. PMID: 16785439 | PMCID: PMC1502541