Folding of Proteins under Mechanical Force

  • Michael Schlierf
  • Matthias Rief


Many proteins in the body are subject to mechanical forces in their natural context. Examples are muscle proteins or proteins of the cytoskeleton. Often a protein faces the challenge of refolding against a mechanical load. Although the unfolding of proteins under load has been extensively investigated, knowledge about refolding mechanics is still rare. This chapter develops a model that describes the effect of an external force on protein folding. The model can provide important help for the design of a single-molecule mechanical experiment. The chapter discusses how spacer length and elasticity, as well as probe spring constant, affect the observed results. In this context it also briefly discusses the difference between atomic force microscope and optical tweezers experiments.


Optical Tweezer Persistence Length Contour Length Folding Rate Atomic Force Microscope Experiment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Schlierf, M., F. Berkemeier, and M. Rief, Direct observation of active protein folding using lock-in force spectroscopy. Biophys J 2007;93(11): 3989–98.CrossRefGoogle Scholar
  2. 2.
    Dyer, R. B., Ultrafast and downhill protein folding. Curr Opin Struct Biol 2007;17(1):38–47.CrossRefGoogle Scholar
  3. 3.
    Cecconi, C., et al., Direct observation of the three-state folding of a single protein molecule. Science 2005;309(5743):2057–60.ADSCrossRefGoogle Scholar
  4. 4.
    Bechtluft, P., et al., Direct observation of chaperone-induced changes in a protein folding pathway. Science 2007;318(5855):1458–61.ADSCrossRefGoogle Scholar
  5. 5.
    Greenleaf, W. J., M. T. Woodside, and S. M. Block, High-resolution, single-molecule measurements of biomolecular motion. Annu Rev Biophys Biomol Struct 2007;36:171–90.CrossRefGoogle Scholar
  6. 6.
    Seol, Y., et al., Elasticity of short DNA molecules: theory and experiment for contour lengths of 0.6–7 micron. Biophys J 2007;93(12):4360–73.CrossRefGoogle Scholar
  7. 7.
    Wen, J.D., et al., Force unfolding kinetics of RNA using optical tweezers. I. Effects of experimental variables on measured results. Biophys J 2007;92(9):2996–3009.ADSCrossRefGoogle Scholar
  8. 8.
    Kedrov, A., et al., Controlled unfolding and refolding of a single sodium-proton antiporter using atomic force microscopy. J Mol Biol 2004;340(5):1143–52.CrossRefGoogle Scholar
  9. 9.
    Fernandez, J. M., and H. Li, Force-clamp spectroscopy monitors the folding trajectory of a single protein. Science 2004;303(5664):1674–8.ADSCrossRefGoogle Scholar
  10. 10.
    Kessler, M., et al., Bacteriorhodopsin folds into the membrane against an external force. J Mol Biol 2006;357(2):644–54.CrossRefGoogle Scholar
  11. 11.
    Lee, G., et al., Nanospring behaviour of ankyrin repeats. Nature 2006;440(7081):246–9.ADSCrossRefGoogle Scholar
  12. 12.
    Bornschlogl, T., and M. Rief, Single molecule unzipping of coiled coils: sequence resolved stability profiles. Phys Rev Lett 2006;96(11):118102.ADSCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Michael Schlierf
    • 1
  • Matthias Rief
    • 1
  1. 1.Physikdepartment E22, TU Mnchen85748 GarchingGermany

Personalised recommendations