Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Muscle force is generated by myosin heads stereospecifically attached to actin

Nature volume 388, pages 186–190 (1997)Cite this article

Abstract

Muscle force is generated by myosin crossbridges interacting with actin. As estimated from stiffness1,2 and equatorial X-ray diffraction3 of muscle and muscle fibres, most myosin crossbridges are attached to actin during isometric contraction, but a much smaller fraction is bound stereospecifically4,5,6,7. To determine the fraction of crossbridges contributing to tension and the structural changes that attached crossbridges undergo when generating force, we monitored the X-ray diffraction pattern during temperature-induced tension rise in fully activated permeabilized frog muscle fibres. Temperature jumps8 from 5–6 °C to 16–19 °C initiated a 1.7-fold increase in tension without significantly changing fibre stiffness or the intensities of the (1,1) equatorial and (14.5 nm)−1 meridional X-ray reflections. However, tension rise was accompanied by a 20% decrease in the intensity of the (1,0) equatorial reflection and an increase in the intensity of the first actin layer line by ∼13% of that in rigor. Our results show that muscle force is associated with a transition of the crossbridges from a state in which they are nonspecifically attached to actin to one in which stereospecifically bound myosin crossbridges label the actin helix.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Time courses (traces from top to bottom) of temperature, change in sarcomere length, tension and intensities of the X-ray reflections I14.5 (□), I1,0 (⋄) and I1,1 (○) during the length-steps and temperature jump (T-jump) protocol.
Figure 2: Normalized tension (continuous line), meridional I14.5 (crosses), equatorial I1,0 (squares) and I1,1 (circles) intensities following the T-jump.
Figure 4: a, Off-meridional X-ray intensities (counts per pixel) integrated along the equator between (35 nm)−1 and 8 nm)−1 and plotted against the meridional spacing.
Figure 3: Two-dimensional diffraction patterns.

Similar content being viewed by others

References

  1. Goldman, Y. E. & Simmons, R. M. Active and rigor muscle stiffness. J. Physiol., Lond. 269, 55P–57P (1977).

    Google Scholar 

  2. Higuchi, H., Yanagida, T. & Goldman, Y. E. Compliance of thin filaments in skinned fibers of rabbit skeletal muscle. Biophys. J. 69, 1000–1010 (1995).

    Article  ADS  CAS  Google Scholar 

  3. Haselgrove, J. C. & Huxley, H. E. X-ray evidence for radial cross-bridge movement and for the sliding filament model in actively contracting skeletal muscle. J. Mol. Biol. 77, 549–568 (1973).

    Article  CAS  Google Scholar 

  4. Huxley, H. E., Faruqi, A. R., Kress, M., Bordas, J. & Koch, M. H. J. Time resolved X-ray diffraction studies of the myosin layer line reflections during muscle contraction. J. Mol. Biol. 158, 637–684 (1982).

    Article  CAS  Google Scholar 

  5. Yagi, N. Intensification of the first actin layer-line during contraction of frog skeletal muscle. Adv. Biophys. 27, 35–43 (1991).

    Article  CAS  Google Scholar 

  6. Amemiya, Y., Wakabayashi, K., Tanaka, H., Ueno, Y. & Miyahara, J. Laser-stimualted luminescence used to measure x-ray diffraction of a contracting striated muscle. Science 237, 164–168 (1987).

    Article  ADS  CAS  Google Scholar 

  7. Bordas, J. et al. Two-dimensional X-ray diffraction of muscle: recent results. Adv. Biophys. 27, 15–33 (1991).

    Article  CAS  Google Scholar 

  8. Bershitsky, S. Y. & Tsaturyan, A. K. Force generation and work production by covalently cross-linked actin-myosin cross-bridges in rabbit muscle fibers. Biophys. J. 69, 1011–1021 (1995).

    Article  ADS  CAS  Google Scholar 

  9. Huxley, H. E. The mechanism of muscular contraction. Science 164, 1356–1366 (1969).

    Article  ADS  CAS  Google Scholar 

  10. Huxley, A. F. & Simmons, R. M. Proposed mechanism of force generation in striated muscle. Nature 233, 533–538 (1971).

    Article  ADS  CAS  Google Scholar 

  11. Huxley, H. E. & Kress, M. Cross-bridge behaviour during muscle contraction. J. Musc. Res. Cell Motility 6, 153–161 (1985).

    Article  CAS  Google Scholar 

  12. Hirose, K., Lenart, T. D., Murray, J. M., Franzini-Armstrong, C. & Goldman, Y. E. Flash and smash: rapid freezing of muscle fibers activated by photolysis of caged ATP. Biophys. J. 65, 397–408 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Ling, N., Shrimpton, C., Sleep, J., Kendrick-Jones, J. & Irving, M. Fluorescent probes of orientation of myosin regulatory light chains in relaxed, rigor and contracting muscle. Biophys. J. 70, 1836–1846 (1996).

    Article  ADS  CAS  Google Scholar 

  14. Ostap, E. M., Barnett, V. A. & Thomas, D. D. Resolution of three structural states of spin-labelled myosin in contracting muscle. Biophys. J. 69, 177–188 (1995).

    Article  ADS  CAS  Google Scholar 

  15. Kress, M., Huxley, H. E., Faruqi, A. R. & Hendrix, J. Structural changes during activation of frog muscle studied by time-resolved X-ray diffraction. J. Mol. Biol. 188, 325–342 (1986).

    Article  CAS  Google Scholar 

  16. Ford, L. E., Huxley, A. F. & Simmons, R. M. Tension responses to sudden length change in stimulated frog muscle fibres near slack length. J. Physiol., Lond. 269, 441–515 (1977).

    Article  CAS  Google Scholar 

  17. Huxley, H. E. et al. Changes in the X-ray reflections from contracting muscle during rapid mechanical transients and their structural implications. J. Mol. Biol. 169, 469–506 (1983).

    Article  CAS  Google Scholar 

  18. Irving, M., Lombardi, V., Piazzesi, G. & Ferenczi, M. A. Myosin head movements are synchronous with the elementary force-generating process in muscle. Nature 357, 156–158 (1992).

    Article  ADS  CAS  Google Scholar 

  19. Lombardi, V., Piazzesi, G., Ferenczi, M. A., Thirlwell, H. & Irving, M. Elastic distortion of myosin heads and repriming of the working stroke in muscle. Nature 374, 553–555 (1995).

    Article  ADS  CAS  Google Scholar 

  20. Piazzesi, G. et al. Changes in the x-ray diffraction pattern from single, intact muscle fibers produced by rapid shortening and stretch. Biophys. J. 68, 92s–98s (1995).

    Article  Google Scholar 

  21. Bershitsky, S. Y. et al. Mechanical and structural properties underlying contraction of skeletal muscle fibers after partial 1-ethyl-[3-(3-dimethylamino)propyl]carbodiimide cross-linking. Biophys. J. 71, 1462–1474 (1996).

    Article  ADS  CAS  Google Scholar 

  22. Vainstain, B. K. Diffraction of X-rays by Chain Molecules (Izdatelstvo Akademii Nauk SSSR, Moscow, (1963)).

    Google Scholar 

  23. Cooke, R., Crowder, M. S., Wendt, C. H., Barnett, V. A. & Thomas, D. D. in Contractile Mechanisms in Muscle 413–423 (Plenum, New York, London, (1984)).

    Book  Google Scholar 

  24. Harford, J. J. & Squire, J. M. Evidence for structurally different attached states of myosin cross-bridges on actin during contraction of fish muscle. Biophys. J. 63, 387–396 (1992).

    Article  ADS  CAS  Google Scholar 

  25. Brenner, B. & Yu, L. C. Structural changes in the actomyosin cross-bridges associated with force generation. Proc. Natl Acad. Sci. USA 90, 5252–5256 (1993).

    Article  ADS  CAS  Google Scholar 

  26. Irving, M. et al. Tilting of the light-chain region of myosin during step length changes and active force generation in skeletal muscle. Nature 375, 688–691 (1995).

    Article  ADS  CAS  Google Scholar 

  27. Martin-Fernandez, M. A. et al. Time-resolved X-ray diffraction studies of myosin head movements in live frog sartorius muscle during isometric and isotonic contractions. J. Musc. Res. Cell Motility 15, 319–348 (1994).

    CAS  Google Scholar 

  28. Towns-Andrews, E. et al. Time-resolved x-ray diffraction station: x-ray optics, detectors and data acquisition. Rev. Scient. Instr. 60, 2346–2349 (1989).

    Article  ADS  CAS  Google Scholar 

  29. Huxley, H. E. & Brown, W. The low-angle X-ray diagram of vertebrate striated muscle and its behaviour during contraction and rigor. J. Mol. Biol. 30, 383–434 (1967).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Irving for comments on the early version of the manuscript, D. R. Trentham for support, and E. Towns-Andrews and the non-crystalline-diffraction team at CLRC Daresbury Laboratory for hard- and sofware support. The work was supported by the MRC and grants from the EU, INTAS, ISF, HHMI, RFBR and by CCP13 of EPSRC and BBSRC.

Author information

Authors and Affiliations

  1. National Institute for Medical Research, Mill Hill, NW7 1AA, London, UK

    Paul Brown, Ronald Burns & Michael A. Ferenczi

  2. *Institute of Physiology, Urals Branch of the Russian Academy of Sciences, 620219, Yekaterinburg, Russia

    Sergey Y. Bershitsky, Olga N. Bershitskaya & Gregory I. Mashanov

  3. †Institute of Mechanics, Lomonosov Moscow University, 119899, Moscow, Russia

    Andrey K. Tsaturyan

Authors
  1. Sergey Y. Bershitsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrey K. Tsaturyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga N. Bershitskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory I. Mashanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ronald Burns
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael A. Ferenczi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael A. Ferenczi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bershitsky, S., Tsaturyan, A., Bershitskaya, O. et al. Muscle force is generated by myosin heads stereospecifically attached to actin. Nature 388, 186–190 (1997). https://doi.org/10.1038/40651

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/40651

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing