FOLDING-UNFOLDING TRANSITIONS IN SINGLE TITIN MOLECULES CHARACTERIZEDWITH LASER TWEEZERS

Titin, a giant filamentous polypeptide, is believed to play a fundamen tal role in maintaining sarcomeric structural integrity and developing what is known as passive force in muscle. Measurements of the force r equired 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-for ce transition at similar to 2.5 piconewtons. A fraction of the molecul e (5 to 40 percent) remains permanently unfolded, behaving as a wormli ke chain with a persistence length (a measure of the chain's bending r igidity) of 20 angstroms. Force hysteresis arises from a difference be tween the unfolding and refolding kinetics of the molecule relative to the stretch and release rates in the experiments, respectively. Scali ng the molecular data up to sarcomeric dimensions reproduced many feat ures of the passive force versus extension curve of muscle fibers.