Mechanics of the Single Myofibril

The single myofibril is the minimum preparation that retains the natural architecture of the sarcomere. As such, it has some important advantages over the larger preparations that also retain the lattice. First, interpretation is direct: measured tension is borne fully and completely by the sarcomeres under observation; thus, tension and sarcomere dynamics can be related to one another without assumption. Second, the preparation is practically molecular in scale. Results can be interpreted mechanistically with fewer hidden assumptions than is true with larger preparations.

Single cardiac myofibril of human heart stained with antibodies to the N2B and N2BA titin isoforms (from Neagoe et al., 2002)

We have completed many studies reporting mechanical properties of single myofibrils. Both active and passive forces have been the focus of attention. We showed that single cardiac myofibrils generate active tension values of ~0.15 N/mm2, comparable to larger cardiac-muscle preparations when the difference in myofibrillar cross-sectional area is considered. The level of passive tension was shown to be similar in single cardiac myofibrils and trabeculae or papillary muscles over a physiological sarcomere-length range from approximately 1.9 to 2.2 µm, indicating the important contribution of myofibrils to the passive stiffness of whole myocardium. The single myofibril was also used to investigate the mechanical properties of titin filaments in vertebrate muscle or titin-like proteins in insect flight muscle; titins were found to be largely responsible for the passive myofibrillar stiffness. In related experiments we applied various models of polymer elasticity theory to mathematically describe the mechanics of titin in the myofibril. We found that the passive tension of single cardiac myofibrils can be reconstituted using parameters obtained in single-molecule AFM mechanics on titin domains. More recently, we have compared the passive tension in single myofibrils of normal and chronically diseased human myocardium; decreased titin-based passive force was seen in myofibrils of failing myocardium. In a different set of experiments, we have used the single-myofibril preparation to measure the titin-based contribution to shortening velocity of skeletal muscle fibers and to quantify the speed of titin elastic recoil in single human cardiac myofibrils.

Single Myofibril Mechanics, Select Studies: 

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., V.I. Popov & G.H. Pollack (1994) Passive and active tension in single cardiac myofibrils. Biophys. J. 67:782-792. 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

Linke, W.A., M. Ivemeyer, P. Mundel, M.R. Stockmeier & B. Kolmerer (1998a) 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 (1998b) 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., 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.

Minajeva, A., C. Neagoe, M. Kulke & W.A. Linke (2002) Titin-based contribution to shortening velocity of rabbit skeletal myofibrils. J. Physiol. 540:177-188. pdf available free from publisher.

Neagoe C., M. Kulke, F. del Monte, J.K. Gwathmey, P.P. de Tombe, R.J. Hajjar & W.A. Linke (2002) Titin isoform switch in ischemic human heart disease. Circulation. 106:1333-1341. free pdf from publisher

Opitz, C.A., M. Kulke, M. C. Leake, C. Neagoe, H. Hinssen, R.J. Hajjar & W.A. Linke (2003) Damped elastic recoil of the titin spring in myofibrils of human myocardium. Proc. Natl. Acad. Sci. USA. 100:12688-12693.  free pdf from pubmed central plus online supplement

Modeling of Myofibrillar Passive Mechanical Properties, Select Studies:

Li H., W.A. Linke, A.F. Oberhauser, M. Carrion-Vazquez, J.G. Kerkvliet, H. Lu, P.E. Marszalek & J.M. Fernandez (2002) Reverse engineering of the giant muscle protein titin. Nature. 418:998-1002. News coverage in J. Cell Biol. and free pdf available here, plus online supplement.

Linke, W.A. & J.M. Fernandez (2002) Cardiac titin: Molecular basis of elasticity and cellular contribution to elastic and viscous stiffness components in myocardium. J. Muscle Res. Cell Motil. 23:483-497. free pdf available here.

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.

Minajeva, A., M. Kulke, J.M. Fernandez & W.A. Linke (2001) Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils. Biophys. J. 80:1442-1451. pdf available free from publisher.

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