Titin elasticity in the context of the sarcomere: force and extensibility measurements on single myofibrils.
Skeletal-muscle titin contains in its I-band section two main elastic elements, stretches of Ig-like domains and the PEVK segment. Both elements contribute to the extensibility and passive force development of relaxed skeletal muscle fibers during stretch. To explore the nature of elasticity of the segments, their force-extension relation was determined with immunofluorescence and immunoelectron microscopy, combined with isolated myofibril mechanics. The results were then fitted with recent models of biopolymer elasticity. Whereas an entropic-spring mechanism may account for the elasticity of the Ig-domain segments, PEVK-titin elasticity appears to have both entropic and enthalpic origins. The modeling explains why the two elements extend sequentially upon stretch: elongation of the Ig-domain regions (with folded modules) is followed by unraveling of the PEVK domain. I-band titin in cardiac muscle is expressed in two main isoforms, N2-A and N2-B. The N2-A isoform is similar to that found in skeletal muscle, whereas the N2-B titin is distinguished by cardiac-specific Ig-motifs and nonmodular sequences within the central I-band section. By examining the extensibility of N2-B titin, it was found that this isoform extends by recruiting three distinct elastic elements: poly-Ig regions and the PEVK domain at low to modest stretch, and in addition, a unique 572-residue sequence insertion at higher physiological stretch. Extension of all three elements allows cardiac titin to stretch fully reversibly at physiological sarcomere lengths, without the need to unfold individual Ig domains.
Linke
W A
WA
Institute of Physiology II, University of Heidelberg, Germany.
D000818:Animals; D064211:Connectin; D004548:Elasticity; D006321:Heart / Q000502:physiology; D009124:Muscle Proteins / Q000737:chemistry* / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology* / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure; D009210:Myofibrils / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000502:physiology; D011494:Protein Kinases / Q000737:chemistry* / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology*; D013816:Thermodynamics
D064211:Connectin; D009124:Muscle Proteins; D020033:Protein Isoforms; D011494:Protein Kinases