Force transmission, compliance, and viscoelasticity are altered in the α₇-integrin-null mouse diaphragm

Abstract

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.

Localization and function of Xinα in mouse skeletal muscle

“…␣ 7 ␤ 1 -Integrin is a transmembrane structural protein concentrated at the MTJ, linking to actin cytoskeleton through talin/vinculin. Alterations in compliance have been observed in ␣ 7 -integrin (Itga7) knockout mouse muscle (38), consistent with the possibility of the ␣ 7 ␤ 1 -integrin being a load-bearing protein. In our previous yeast two-hybrid study, we showed that mXin␣ interacted with vinculin and filamin (10).…”

Loss of the α7 Integrin Promotes Extracellular Signal-Regulated Kinase Activation and Altered Vascular Remodeling

“…Reduced compliance was also observed in diaphragm muscle from 1-year-old ␣7 integrinnull mice. 32 Changes in the deposition and/or composition of extracellular matrix or expression of the repertoire of integrins in vascular smooth muscle may contribute to this phenotype.…”

Severe muscular dystrophy in mice that lack dystrophin and α7 integrin

“…Mutations in the ␣7-integrin gene are responsible for human congenital myopathy, in which patients exhibit delayed motor milestones (Hayashi et al, 1998). Mice that lack ␣7 integrin develop myopathy and demonstrate altered force transmission, compliance and viscoelasticity in diaphragm muscle (Lopez et al, 2005;Mayer et al, 1997). In addition, ␣7␤1 integrin plays an important role in the development of NMJs (Burkin et al, 1998;Burkin et al, 2000) and MTJs (Mayer et al, 1997;Nawrotzki et al, 2003).…”