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Science 16 May 1997:
Vol. 276. no. 5315, pp. 1112 - 1116
DOI: 10.1126/science.276.5315.1112
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Folding-Unfolding Transitions in Single Titin Molecules Characterized with Laser Tweezers

Miklós S. Z. Kellermayer, *dagger Steven B. Smith, * Henk L. Granzier, ddagger Carlos Bustamante *

Titin, a giant filamentous polypeptide, is believed to play a fundamental role in maintaining sarcomeric structural integrity and developing what is known as passive force in muscle. Measurements of the force required to stretch a single molecule revealed that titin behaves as a highly nonlinear entropic spring. The molecule unfolds in a high-force transition beginning at 20 to 30 piconewtons and refolds in a low-force transition at ~2.5 piconewtons. A fraction of the molecule (5 to 40 percent) remains permanently unfolded, behaving as a wormlike chain with a persistence length (a measure of the chain's bending rigidity) of 20 angstroms. Force hysteresis arises from a difference between the unfolding and refolding kinetics of the molecule relative to the stretch and release rates in the experiments, respectively. Scaling the molecular data up to sarcomeric dimensions reproduced many features of the passive force versus extension curve of muscle fibers.

M. S. Z. Kellermayer and H. L. Granzier, Department of Veterinary Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164-6520, USA.
S. B. Smith and C. Bustamante, Howard Hughes Medical Institute, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
*   These authors contributed equally to this work.

dagger    Present address: Central Laboratory, University Medical School of Pecs, Hungary.

ddagger    To whom correspondence should be addressed.

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