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The molecular elasticity of the extracellular matrix protein tenascin

Nature volume 393, pages 181–185 (1998)Cite this article

Abstract

Extracellular matrix proteins are thought to provide a rigid mechanical anchor that supports and guides migrating and rolling cells1,2,3,4. Here we examine the mechanical properties of the extracellular matrix protein tenascin by using atomic-force-microscopy techniques. Our results indicate that tenascin is an elastic protein. Single molecules of tenascin could be stretched to several times their resting length. Force–extension curves showed a saw-tooth pattern, with peaks of force at 137 pN. These peaks were ∼25 nm apart. Similar results have been obtained by study of titin5. We also found similar results by studying recombinant tenascin fragments encompassing the 15 fibronectin type III domains of tenascin. This indicates that the extensibility of tenascin may be due to the stretch-induced unfolding of its fibronectin type III domains. Refolding of tenascin after stretching, observed when the force was reduced to near zero, showed a double-exponential recovery with time constants of 42 domains refolded per second and 0.5 domains per second. The former speed of refolding is more than twice as fast as any previously reported speed of refolding of a fibronectin type III domain6,7. We suggest that the extensibility of the modular fibronectin type III region may be important in allowing tenascin–ligand bonds to persist over long extensions. These properties of fibronectin type III modules may be of widespread use in extracellular proteins containing such domain8,9.

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Figure 1: Force–extension relationships for native tenascin hexabrachions measured with AFM techniques.
Figure 2: The WLC model, using a persistence length of p = 0.42 nm and a contour length increment of Δlc = 28.5 nm, describes the force–extension curves of recombinant tenascin fragments.
Figure 3: Repeated unfolding/refolding cycles of a single recombinant TNfnALL protein.
Figure 4: Repeated refolding cycles of a single TNfnAll protein using a double-pulse experiment (inset) identifies at least two refolding rate constants.
Figure 5: A Monte Carlo simulation shows that tandem FN-III repeats can extend the range and lifetime of a protein–ligand bond and reduce the force required to break it (see Methods).

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Mayo Foundation, Rochester, 55905, Minnesota, USA

    Andres F. Oberhauser, Piotr E. Marszalek & Julio M. Fernandez

  2. Department of Cell Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Harold P. Erickson

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  1. Andres F. Oberhauser
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  2. Piotr E. Marszalek
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  3. Harold P. Erickson
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  4. Julio M. Fernandez
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Correspondence to Julio M. Fernandez.

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Oberhauser, A., Marszalek, P., Erickson, H. et al. The molecular elasticity of the extracellular matrix protein tenascin. Nature 393, 181–185 (1998). https://doi.org/10.1038/30270

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