Folding-Unfolding Transitions in Single Titin Molecules Characterized with Laser Tweezers
Miklós S. Z. Kellermayer,
*
Steven B. Smith,
*
Henk L. Granzier,
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.
Present address: Central Laboratory, University Medical School
of Pecs, Hungary.
To whom correspondence should be addressed.
