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.
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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 |
Agianian, B., U. Krzic, F. Qiu, W.A. Linke, K Leonard & B. Bullard (2004) A troponin switch that regulates muscle contraction by stretch instead of calcium. EMBO J. 23:772-779. free pdf from Pubmed Central
Kulke, M., C. Neagoe, B. Kolmerer, A. Minajeva, H. Hinssen, B. Bullard & W.A. Linke (2001) Kettin, a major source of myofibrillar stiffness in Drosophila indirect flight muscle. J. Cell Biol. 154:1045-1057. News coverage in J. Cell Biol. and pdf available free from publisher.
Linke, W.A., D.E. Rudy, T. Centner, M. Gautel, C. Witt, S. Labeit & C.C. Gregorio (1999) I-band titin in cardiac muscle is a three-element molecular spring and is critical for maintaining thin filament structure. J. Cell Biol. 146:631-644. pdf available free from publisher.
Linke, W.A., M. Ivemeyer, P. Mundel, M.R. Stockmeier & B.
Kolmerer (1998) Nature of
PEVK-titin elasticity in skeletal muscle. Proc.
Natl. Acad. Sci. USA. 95:8052-8057. pdf
available free from
publisher.
Linke, W.A., M.R. Stockmeier, M. Ivemeyer, H. Hosser & P. Mundel (1998) Characterizing titin's I-band Ig domain region as an entropic spring. J. Cell Sci. 111:1567-1574. pdf available free from publisher.
Linke, W.A., M. Ivemeyer, S. Labeit, H. Hinssen, J.C. Rüegg & M. Gautel (1997) Actin-titin interaction in cardiac myofibrils: Probing a physiological role. Biophys. J. 73:905-919. free pdf from Pubmed Central
Linke, W.A., M. Ivemeyer, N. Olivieri, B. Kolmerer, J.C. Rüegg
& S. Labeit (1996) Towards a
molecular understanding of the elasticity of titin. J. Mol.
Biol. 261:62-71. free pdf
here