Cell Biology of Vertebrate and Invertebrate Muscle

We are interested in finding out how titin or titin-like proteins act together with actin, myosin, and many other cytoskeletal proteins to perform the important tasks of scaffolding, mechanical sensing and force generation. Particular attention is paid to vertebrate cardiac muscle cells and the asynchronous fibers of the indirect flight muscle of insects such as Drosophila (fruit fly) and Lethocerus (water bug). A variety of cell biological and biochemical approaches is used, such as immunoelectron microscopy and immunofluorescence microscopy, blotting techniques, cell culture and transfection methods, often in conjunction with mechanical sensing techniques.

Actin (red) and myosin (green) in embryonic chick cardiac myocytes (Linke et al., 1999)

Not the Amazon rain forest, but staining of collagen (C), titin (T), in human heart tissue

Antibody-labeled titin in cultured (beating) neonatal rat cardiac cells

Select publications

  1. A troponin switch that regulates muscle contraction by stretch instead of calcium
    Agianian, B., U. Krzic, F. Qiu, W.A. Linke, K Leonard & B. Bullard , EMBO J. (2004) , 23 , 772-779

  2. Kettin, a major source of myofibrillar stiffness in Drosophila indirect flight muscle
    Kulke, M., C. Neagoe, B. Kolmerer, A. Minajeva, H. Hinssen, B. Bullard & W.A. Linke , J. Cell Biol. (2001) , 154 , 1045-1057

  3. I-band titin in cardiac muscle is a three-element molecular spring and is critical for maintaining thin filament structure
    Linke, W.A., D.E. Rudy, T. Centner, M. Gautel, C. Witt, S. Labeit & C.C. Gregorio , J. Cell Biol. (1999) , 146 , 631-644

  4. Nature of PEVK-titin elasticity in skeletal muscle
    Linke, W.A., M. Ivemeyer, P. Mundel, M.R. Stockmeier & B. Kolmerer , Proc. Natl. Acad. Sci. USA. (1998) , 95 , 8052-8057

  5. Characterizing titin's I-band Ig domain region as an entropic spring
    Linke, W.A., M.R. Stockmeier, M. Ivemeyer, H. Hosser & P. Mundel , J. Cell Sci. (1998) , 111 , 1567-1574

  6. Actin-titin interaction in cardiac myofibrils: Probing a physiological role
    Linke, W.A., M. Ivemeyer, S. Labeit, H. Hinssen, J.C. Rüegg & M. Gautel , Biophys. J. (1997) , 73 , 905-919

  7. Towards a molecular understanding of the elasticity of titin
    Linke, W.A., M. Ivemeyer, N. Olivieri, B. Kolmerer, J.C. Rüegg & S. Labeit , J. Mol. Biol. (1996) , 261 , 62-71