Folding-unfolding transitions in single titin molecules characterized with laser tweezers.
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 approximately 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.
Kellermayer
M S
MS
Department of Veterinary Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, WA 99164-6520, USA.
Smith
S B
SB
Granzier
H L
HL
Bustamante
C
C
D000595:Amino Acid Sequence; D064211:Connectin; D004548:Elasticity; D019277:Entropy; D007136:Immunoglobulins / Q000737:chemistry; D007834:Lasers; D008956:Models, Chemical; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000737:chemistry*; D009126:Muscle Relaxation; D018482:Muscle, Skeletal / Q000737:chemistry / Q000502:physiology; D011489:Protein Denaturation; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D013314:Stress, Mechanical
D064211:Connectin; D007136:Immunoglobulins; D009124:Muscle Proteins; D011494:Protein Kinases