Site and mechanics of failure in normal and dystrophin-deficient skeletal muscle.

Partial or complete tearing of skeletal muscle occurs both in acute muscle injury and in some pathological muscle conditions. Despite the impact of such tearing on normal muscle function, few studies have examined the site or mechanism of muscle injury at cellular or subcellular levels of organization. The present study determines the ultrastructural location and mechanical conditions of tensile failure in normal mouse extensor digitorum longus muscles. All of these muscles failed near a myotendinous junction (MTJ), but within the muscle fibers, in a transverse plane coincident with the edge of an A-band. The breaking stress averaged 5.71 x 10(5) N/m2 for muscles stimulated tetanically during lengthening, and 5.01 x 10(5) N/m2 for unstimulated muscles. Breaking strain averaged 135%, and showed no dependence on the state of activation of the muscle. The energy absorbed by each muscle averaged 362.5 mJ/g in unstimulated muscle, and 613.2 mJ/g in the stimulated samples. In addition to the failure properties of normal muscle, the effect of dystrophin deficiency on the site and conditions of failure was determined using muscle from mdx mice, which lack dystrophin. The absence of dystrophin had no detectable effect on the stress, strain, or energy absorbed, regardless of the state of muscle activation. Unstimulated mdx muscle failed in the plane of an A-band, but tetanic stimulation produced failure in the reticular lamina of the tendon, just external to the MTJ, in 75% of the fibers in the mdx muscles. Although dystrophin's cytoplasmic location makes it unlikely that this unique mode of failure is due directly to the absence of the protein, failure in the reticular lamina may result from a difference in load distribution that accompanies the response of mdx muscle to dystrophin deficiency.