Sarcomere model

Studies on muscle contraction carried out between 1930 and 1960 heralded the modem era of research on cytoskeletal stmctures. Actin and myosin were identified as the major contractile proteins of muscle, and detailed electron microscopic studies on sarcomeres by H.E. Huxley and associates in the 1950s produced the concept of the sliding filament model, which remains the keystone to an understanding of the molecular mechanisms responsible for cytoskeletal motility. 

The sliding filament model describes the mechanism involved in muscle contraction. In this model, sarcomeres become shorter when the thin and thick filaments slide alongside each other and telescope together, with ATP being consumed. During contraction, the following reaction cycle is repeated several times ... 

The "rowing model" is generally accepted, but other quite different processes have been proposed to account for the elementary cycle of muscle contraction. Muscle contracts nearly isovolumetrically thus, anything that expands the sarcomere will cause a contraction. 

The sliding-filament model of muscle contraction. During contraction, the thick and thin filaments slide past each other so that the overall length of the sarcomere becomes shorter. 

An early test of the sliding filament model was the very careful measurement by Gordon et al. (1966) of the active tension produced by the muscle at different sarcomere lengths (Fig. 7B-D). If the myosin heads or crossbridges act as independent force generators, then, as the sarcomere length... 

Fig. 13. The titin Z-repeats and a Z-band assembly model. The N-termini of titin filaments from adjoining sarcomeres overlap in the Z-band. This part of titin comprises a modular region of so-called Z-repeats, each about 45 residues long, the number of which is related to fiber type 24 repeats occur in fast muscles, 57 occur in slow and cardiac muscles. This correlates with the Z-band appearance since fast and slow fibers have narrow and wide Z-bands, respectively, as shown in Fig. 12. The measured axial spacing between a-actinin bridges is about 19.2 nm (Luther and Squire, 2002), a distance that is too long for a single Z-repeat (A) to stretch to. Perhaps the bridge separation is related to two levels of Z-repeats (C).

Fig. 14. Stereo pairs of the transverse structure (A) and the axial structure (B) of a 3D model relating successive half sarcomeres in vertebrate-striated muscles. In both images, the wide blue and brown cylinders represent actin filaments, the gray cross-links...

The two-filament model of the sarcomere was proposed half a century ago (Huxley and Hanson, 1954 Huxley and Niedergerke, 1954) and has been proved to be highly successful in explaining many features of contracting muscle. However, it was realized early that the model is unable to... 

The interaction between actin and myosin filaments in the A-band of the sarcomere is responsible for the muscle contraction (shding-fllament model). 

The sliding filament model explains the molecular basis by which muscular contraction occurs. During muscular contraction, thin filaments within the sarcomere of a myofibril are pulled towards the center of the sarcomere (called the H zone) by the thick filaments. In the process, the sarcomeric length shortens and the myofibril shortens. As a result, the muscle contracts (see Figure 8.11). Steps in the process include the following ... 

Description of muscle contraction has essentially evolved into two separate approaches — lumped whole muscle models and specialized crossbridge models of the sarcomere. The former seek to interpret muscle s complex mechanical properties with a single set of model elements. Muscle experiments measure muscle force and length subjected to isometric (fixed length) conditions, isotonic (fixed load) conditions, and transient analysis where either length or load is rapidly changed. 

Muscle force generation is believed to arise from the formation of crossbridge bonds between thick and thin myofilaments within the basic building block of muscle, the sarcomere. These structures, in the nanometer to micrometer range, must be viewed by electron microscopy or x-ray diffraction, limiting study to fixed, dead material. Consequently, muscle contraction at the sarcomere level must be described by models that integrate metabolic and structural information. 

Crossbridge models focus on mechanics at the sarcomere level. Prior to actual observation of crossbridge bonds, Huxley [28] proposed a model whereby contractile force is generated by the formation of crossbridge bonds between myofilaments. This model was subsequently shown unable to describe... 

FIGURE 8.13 Schematic representation of a muscle fiber composed of N series sarcomeres each with M parallel pairs of active, viscoelastic bonds. Each bond is described by a three-element viscoelastic model. (Adapted from Palladino, J.L. and Noordergraaf, A. 1998. Springer-Verlag, New York, pp. 33-57.)... 

---