Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils.
The elastic section of the giant muscle protein titin contains many immunoglobulin-like domains, which have been shown by single-molecule mechanical studies to unfold and refold upon stretch-release. Here we asked whether the mechanical properties of Ig domains and/or other titin regions could be responsible for the viscoelasticity of nonactivated skeletal-muscle sarcomeres, particularly for stress relaxation and force hysteresis. We show that isolated psoas myofibrils respond to a stretch-hold protocol with a characteristic force decay that becomes more pronounced following stretch to above 2.6-microm sarcomere length. The force decay was readily reproducible by a Monte Carlo simulation taking into account both the kinetics of Ig-domain unfolding and the worm-like-chain model of entropic elasticity used to describe titin's elastic behavior. The modeling indicated that the force decay is explainable by the unfolding of only a very small number of Ig domains per titin molecule. The simulation also predicted that a unique sequence in titin, the PEVK domain, may undergo minor structural changes during sarcomere extension. Myofibrils subjected to 1-Hz cycles of stretch-release exhibited distinct hysteresis that persisted during repetitive measurements. Quick stretch-release protocols, in which variable pauses were introduced after the release, revealed a two-exponential time course of hysteresis recovery. The rate constants of recovery compared well with the refolding rates of Ig-like or fibronectin-like domains measured by single-protein mechanical analysis. These findings suggest that in the sarcomere, titin's Ig-domain regions may act as entropic springs capable of adjusting their contour length in response to a stretch.
Institute of Physiology and Pathophysiology, University of Heidelberg, D-69120 Heidelberg, Germany.
A
A
Minajeva
M
M
Kulke
J M
JM
Fernandez
W A
WA
Linke
D000595:Amino Acid Sequence; D000818:Animals; D064211:Connectin; D004548:Elasticity; D007700:Kinetics; D008954:Models, Biological; D009010:Monte Carlo Method; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000737:chemistry* / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009210:Myofibrils / Q000502:physiology* / Q000648:ultrastructure; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry* / Q000502:physiology*; D051381:Rats; D013314:Stress, Mechanical; D013997:Time Factors; D014783:Viscosity
D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases