Titin-induced force enhancement and force depression: a 'sticky-spring' mechanism in muscle contractions?
The sliding filament and crossbridge theories do not suffice to explain a number of muscle experiments. For example, from the entire muscle to myofibrils, predictions of these theories were shown to underestimate the force output during and after active tissue stretch. The converse applies to active tissue shortening. In addition to the crossbridge cycle, we propose that another molecular mechanism is effective in sarcomere force generation. We suggest that, when due to activation, myosin binding sites are available on actin, the giant protein titin's PEVK region attaches itself to the actin filament at those sites. As a result, the molecular spring length is dramatically reduced. This leads to increased passive force when the sarcomere is stretched and to decreased or even negative passive force when the sarcomere shortens. Moreover, during shortening, the proposed mechanism interferes with active-force production by inhibiting crossbridges. Incorporation of a simple 'sticky-spring' mechanism model into a Hill-type model of sarcomere dynamics offers explanations for several force-enhancement and force-depression effects. For example, the increase of the sarcomere force compared to the force predicted solely by the sliding filament and crossbridge theories depends on the stretch amplitude and on the working range. The same applies to the decrease of sarcomere force during and after shortening. Using only literature data for its parameterization, the model predicts forces similar to experimental results.
Rode
Christian
C
Institute of Motion Science, Friedrich Schiller University, Seidelstr. 20, 07749 Jena, Germany. christian.rode@uni-jena.de
Siebert
Tobias
T
Blickhan
Reinhard
R
D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000378:metabolism; D000818:Animals; D064211:Connectin; D004548:Elasticity; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology
D000199:Actins; D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases