Research Interests
• Molecular regulation and mechanico-chemistry of contraction in skeletal
and cardiac muscle
• Mechanisms by which muscle length has an effect on contractile output
Contact Information
Department of Bioengineering
University of Washington
Box 355061
William H. Foege Building, Room N310E
Phone: 206-543-4478, 206-543-0834
Fax: 206-685-3300
E-mail: dmartyn@u.washington.edu
Research Description
The relation between protein structure, interaction and function determines to a great extent the properties and function of cells. Muscle is an excellent system for studying these interactions because mechanical, biochemical, optical and thermodynamic measurements can be made in a system composed of an array of complex but highly organized proteins. In addition, the regulation of protein interactions leading to muscle contraction involves the binding of an intracellular "second messenger", calcium, to a complex system of regulatory proteins, which display a high degree of cooperative interaction. The isolation, characterization, modification by recombinant DNA technology and incorporation back into muscle cells of some to these proteins is beginning to allow the elucidation of the detailed relation between protein conformation, ligand-binding and regulatory function.
The major thrusts of our research have been to understand the mechanisms by which muscle length has a profound effect on contractile output, particularly in cardiac muscle. To attain this goal we have undertaken studies to determine the length dependence of contractile properties in papillary muscles from the right ventricles of ferrets. Our results have led us to believe the length has a large effect on some aspect of myofilament calcium activation. To determine a detailed molecular mechanism we are conducting experiments involving mechanically and chemically skinned (cells with no surface membranes) skeletal and cardiac muscle preparations. These studies involve the measurement of force-calcium-length relations under various biochemical and ionic conditions, the extraction and substitution of calcium regulatory proteins, fluorescent labeling of regulatory proteins to monitor calcium induced conformational changes and chemical modification of the basic actin-myosin interaction. To determine the nature and roles of interactions of muscle regulatory proteins we modify protein structure using site directed mutagengenesis and measure the change in function when the modified proteins are reconstituted into the muscle preparations.
Teaching Activities
- BIOEN 304: Intro to Bioengineering Physiology I
Selected Publications
- Warner-Clemmens, E.W., M. Entezari, D.A. Martyn and M. Regnier. 2005. Different effects of cardiac vs. skeletal muscle regulatory proteins on in vitro measurements of actin filament speed and force. J. Physiol. (in Press).
- Martyn, D.A. 2004. Invited editorial. Myosin-binding protein C: structural and functional complexity. J. Mol. Cardiol. 37: 813-815.
- Adhikari, B.B., M. Regnier, A.J. Rivera, K.L. Kreutziger and D.A. Martyn. 2004. Cardiac length dependence of force and force redevelopment kinetics with altered crossbridge cycling. Biophys. J 87: 1784-1794.
- Regnier, M., H. Martin, R.J. Barsotti, D.A. Martyn and E. Clemmens. 2004. Crossbridge vs. thin filament contributions to the level and rate of force development in cardiac muscle. Biophys. J. 87: 1815-1824.
- Martyn, D.A., B. Adhikari, M. Regnier, J. Gu, S. Xu and L.C. Yu. 2004. Response of equatorial X-ray reflections and stiffness to altered sarcomere length and myofilament lattice spacing in relaxed skinned cardiac muscle. Biophys. J. 86: 1-10.
- Kohler, J., Y. Chen, B. Brenner, A.M. Gordon, T. Kraft, D.A. Martyn, M. Regnier, A.J. Rivera, C.K. Wang and P.B. Chase. 2003. Familial hypertrophic cardiomyopathy mutations in troponin I (K182(, G203S, K206Q) enhance filament sliding. Physiol. Genom. 14: 117-128.
- Martyn, D.A., P.B. Chase, M. Regnier and A.M. Gordon. 2002. A simple model of myofilament compliance predicts activation dependent crossbridge kinetics in skinned skeletal fibers. Biophys. J. 83: 3425-3434.
- Martyn, D.A. and A.M. Gordon. 2001. Influence of length on force and activation dependent changes in cTnC structure in skinned cardiac and fast skeletal muscle. Biophys. J. 80: 2798-2808.
- Martyn, D.A., M. Regnier, D. Xu and A.M. Gordon. 2001. Ca2+ and crossbridge dependent changes in N- and C-terminal structure of troponin C in rat cardiac muscle. Biophys. J. 80: 360-370.
- Regnier, M., P.B. Chase and D.A. Martyn. 1999. Contractile properties of rabbit psoas fibres inhibited by berylium fluoride. J. Musc. Res. Cell. Motil. 20: 425-432.
- Martyn, D.A., C.J. Freitag and A.M. Gordon. 1999. Ca2+ and crossbridge induced changes in troponin C in skinned skeletal muscle fibers: effects of force inhibition. Biophys. J. 76: 1480-1493.
- Martyn, D.A. and P.Bryant Chase. 1995. Faster force transients at sub-maximal Ca2+-activation of skinned psoas fibers from rabbit. Biophys. J. 68: 235-242.
- Martyn, D.A., P.B. Chase and J.D. Hannon, L.L. Huntsman, M.J. Kushmerick and A.M. Gordon. 1994. Unloaded shortening of skinned muscle fibers from rabbit activated with and without Ca2+. Biophys. J. 67: 1984-1993.
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