Alpha7beta1 integrin is a transmembrane structural and receptor protein of skeletal muscles, and the absence of alpha7-integrin causes muscular dystrophy. We hypothesized that the absence of alpha7-integrin alters compliance and viscoelasticity and disrupts the mechanical coupling between passive transverse and axial contractile elements in the diaphragm. In vivo the diaphragm is loaded with pressure, and therefore axial and transverse length-tension relationships are important in assessing its function. We determined diaphragm passive length-tension relationships and the viscoelastic properties of its muscle in 1-month-old alpha7-integrin-null mice and age-matched controls. Furthermore, we measured the isometric contractile properties of the diaphragm from mutant and normal mice in the absence and presence of passive force applied in the transverse direction to fibers in 1-month-old and 5-month-old mutant mice. We found that compared with controls, the diaphragm direction of alpha7-integrin-null mutants showed 1) a significant decrease in muscle extensibility in 1-year-old mice, whereas muscle extensibility increased in the 1-month-old mice; 2) altered muscle viscoelasticity in the transverse direction of the muscle fibers of 1-month-old mice; 3) a significant increase in force-generating capacity in the diaphragms of 1-month-old mice, whereas in 5-month-old mice muscle contractility was depressed; and 4) significant reductions in mechanical coupling between longitudinal and transverse properties of the muscle fibers of 1-month-old mice. These findings suggest that alpha7-integrin serves an important mechanical function in the diaphragm by contributing to passive compliance, viscoelasticity, and modulation of its muscle contractile properties.
Alpha-sarcoglycan (ASG) is a transmembrane protein of the dystrophin-associated complex, and absence of ASG causes limb-girdle muscular dystrophy. We hypothesize that disruption of the sarcoglycan complex may alter muscle extensibility and disrupt the coupling between passive transverse and axial contractile elements in the diaphragm. We determined the length-tension relationships of the diaphragm of young ASG-deficient mice and their controls during uniaxial and biaxial loading. We also determined the isometric contractile properties of the diaphragm muscles from mutant and normal mice in the absence and presence of passive transverse stress. We found that the diaphragm muscles of the null mutants for the protein ASG show 1) significant decrease in muscle extensibility in the directions of the muscle fibers and transverse to fibers, 2) significant reductions in force-generating capacity, and 3) significant reductions in coupling between longitudinal and transverse properties. Thus these findings suggest that the sarcoglycan complex serves a mechanical function in the diaphragm by contributing to muscle passive stiffness and to the modulation of the contractile properties of the muscle.
The role of extracellular elements on the mechanical properties of skeletal muscles is unknown. Merosin is an essential extracellular matrix protein that forms a mechanical junction between the sarcolemma and collagen. Therefore, it is possible that merosin plays a role in force transmission between muscle fibers and collagen. We hypothesized that deficiency in merosin may alter passive muscle stiffness, viscoelastic properties, and contractile muscle force in skeletal muscles. We used the dy/dy mouse, a merosin-deficient mouse model, to examine changes in passive and active muscle mechanics. After mice were anesthetized and the diaphragm or the biceps femoris hindlimb muscle was excised, passive length-tension relationships, stress-relaxation curves, or isometric contractile properties were determined with an in vitro biaxial mechanical testing apparatus. Compared with controls, extensibility was smaller in the muscle fiber direction and the transverse fiber direction of the mutant mice. The relaxed elastic modulus was smaller in merosin-deficient diaphragms compared with controls. Interestingly, maximal muscle tetanic stress was depressed in muscles from the mutant mice during uniaxial loading but not during biaxial loading. However, presence of transverse passive stretch increases maximal contractile stress in both the mutant and normal mice. Our data suggest that merosin contributes to muscle passive stiffness, viscoelasticity, and contractility and that the mechanism by which force is transmitted between adjacent myofibers via merosin possibly in shear.
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