A 2D Finite Element Model of Lateral Transmission of Force in Skeletal Muscle

Author(s):  
Chi Zhang ◽  
Yingxin Gao

Skeletal muscle has a complex hierarchical structure which is mainly composed of myofibers and the surrounding extracellular matrix (ECM) including endomysium, perimysium, and epimysium. Myofibers are long, cylindrical, multinucleated cells composed of repeating sarcomeres, which are basic functional units for skeletal muscle contraction. In order to produce body movement, the force generated by myofiber has to be transmitted from individual fiber to the tendon. The commonly accepted site for force transmission is the myotendinous junction (MTJ) where the myofibers connect to the tendon. However, the myofibers mainly end within the muscle fascicles without reaching the MTJ in many muscles, in which case the force has to be transmitted laterally to adjacent fiber through shear and to the tendon eventually.

Author(s):  
Chi Zhang ◽  
Yingxin Gao

Skeletal muscle has a complex hierarchical structure which is mainly composed of myofibers and the surrounding extracellular matrix (ECM) including endomysium, perimysium, and epimysium. To produce movement, force generated by individual myofibers has to be transmitted to the tendon. Previous studies have shown that many muscle fibers terminate within the fascicle without reaching either ends of the tendon[1,2], in which case force generated has to be transmitted laterally through the ECM to surrounding fibers and then to the tendon[3]. In this study, a two dimensional finite element (FE) model of a single muscle fiber was developed to determine the effects of ECM stiffness and tapered end angles of myofiber on lateral transmission of force in skeletal muscle.


2000 ◽  
Vol 113 (20) ◽  
pp. 3583-3591 ◽  
Author(s):  
M. Fluck ◽  
V. Tunc-Civelek ◽  
M. Chiquet

Tenascin-C and tenascin-Y are two structurally related extracellular matrix glycoproteins that in many tissues show a complementary expression pattern. Tenascin-C and the fibril-associated minor collagen XII are expressed in tissues bearing high tensile stress and are located in normal skeletal muscle, predominantly at the myotendinous junction that links muscle fibers to tendon. In contrast, tenascin-Y is strongly expressed in the endomysium surrounding single myofibers, and in the perimysial sheath around fiber bundles. We previously showed that tenascin-C and collagen XII expression in primary fibroblasts is regulated by changes in tensile stress. Here we have tested the hypothesis that the expression of tenascin-C, tenascin-Y and collagen XII in skeletal muscle connective tissue is differentially modulated by mechanical stress in vivo. Chicken anterior latissimus dorsi muscle (ALD) was mechanically stressed by applying a load to the left wing. Within 36 hours of loading, expression of tenascin-C protein was ectopically induced in the endomysium along the surface of single muscle fibers throughout the ALD, whereas tenascin-Y protein expression was barely affected. Expression of tenascin-C protein stayed elevated after 7 days of loading whereas tenascin-Y protein was reduced. Northern blot analysis revealed that tenascin-C mRNA was induced in ALD within 4 hours of loading while tenascin-Y mRNA was reduced within the same period. In situ hybridization indicated that tenascin-C mRNA induction after 4 hours of loading was uniform throughout the ALD muscle in endomysial fibroblasts. In contrast, the level of tenascin-Y mRNA expression in endomysium appeared reduced within 4 hours of loading. Tenascin-C mRNA and protein induction after 4–10 hours of loading did not correlate with signs of macrophage infiltration. Tenascin-C protein decreased again with removal of the load and nearly disappeared after 5 days. Furthermore, loading was also found to induce expression of collagen XII mRNA and protein, but to a markedly lower level, with slower kinetics and only partial reversibility. The results suggest that mechanical loading directly and reciprocally controls the expression of extracellular matrix proteins of the tenascin family in skeletal muscle.


2021 ◽  
Author(s):  
Marilyne Malbouyres ◽  
Alexandre Guiraud ◽  
Christel Lefrancois ◽  
Melanie Salamito ◽  
Pauline Nauroy ◽  
...  

Although the myotendinous junction (MTJ) is essential for skeletal muscle integrity, its contribution to skeletal muscle function remains largely unknown. Here, we show that CRISPR-Cas9-mediated gene ablation of the MTJ marker col22a1 in zebrafish identifies two distinctive phenotypic classes: class 1 individuals reach adulthood with no overt muscle phenotype while class 2 display severe movement impairment and eventually dye before metamorphosis. Yet mutants that are unequally affected are all found to display defective force transmission attributed to a loss of ultrastructural integrity of the MTJ and myosepta, though with distinct degrees of severity. The behavior-related consequences of the resulting muscle weakness similarly reveal variable phenotypic expressivity. Movement impairment at the critical stage of swimming postural learning eventually causes class 2 larval death by compromising food intake while intensive exercise is required to uncover a decline in muscle performance in class 1 adults. By confronting MTJ gene expression compensation and structural, functional and behavioral insights of MTJ dysfunction, our work unravels variable expressivity of col22a1 mutant phenotype. This study also underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease.


2008 ◽  
Vol 294 (5) ◽  
pp. C1175-C1182 ◽  
Author(s):  
Jianlin Zhang ◽  
Marie-Louise Bang ◽  
David S. Gokhin ◽  
Yingchun Lu ◽  
Li Cui ◽  
...  

Syncoilin is a striated muscle-specific intermediate filament-like protein, which is part of the dystrophin-associated protein complex (DPC) at the sarcolemma and provides a link between the extracellular matrix and the cytoskeleton through its interaction with α-dystrobrevin and desmin. Its upregulation in various neuromuscular diseases suggests that syncoilin may play a role in human myopathies. To study the functional role of syncoilin in cardiac and skeletal muscle in vivo, we generated syncoilin-deficient ( syncoilin−/−) mice. Our detailed analysis of these mice up to 2 yr of age revealed that syncoilin is entirely dispensable for cardiac and skeletal muscle development and maintenance of cellular structure but is required for efficient lateral force transmission during skeletal muscle contraction. Notably, syncoilin−/− skeletal muscle generates less maximal isometric stress than wild-type (WT) muscle but is as equally susceptible to eccentric contraction-induced injury as WT muscle. This suggests that syncoilin may play a supportive role for desmin in the efficient coupling of mechanical stress between the myofibril and fiber exterior. It is possible that the reduction in isometric stress production may predispose the syncoilin skeletal muscle to a dystrophic condition.


2013 ◽  
Vol 115 (6) ◽  
pp. 884-891 ◽  
Author(s):  
Max E. Davis ◽  
Jonathan P. Gumucio ◽  
Kristoffer B. Sugg ◽  
Asheesh Bedi ◽  
Christopher L. Mendias

The extracellular matrix (ECM) of skeletal muscle and tendon is composed of different types of collagen molecules that play important roles in the transmission of forces throughout the body, and in the repair and regeneration of injured tissues. Fibroblasts are the primary cells in muscle and tendon that maintain, repair, and modify the ECM in response to mechanical loading, injury, and inactivity. Matrix metalloproteinases (MMPs) are enzymes that digest collagen and other structural molecules, which are synthesized and excreted by fibroblasts. MMPs are required for baseline ECM homeostasis, but disruption of MMP regulation due to injury or disease can alter the normal ECM architecture and prevent proper force transmission. Chronic injuries and diseases of muscles and tendons can be severely debilitating, and current therapeutic modalities to enhance healing are quite limited. This review will discuss the mechanobiology of MMPs, and the potential use of MMP inhibitors to improve the treatment of injured and diseased skeletal muscle and tendon tissue.


2020 ◽  
Vol 82 (1) ◽  
pp. 485-506 ◽  
Author(s):  
Alexander G. Robling ◽  
Lynda F. Bonewald

Osteocytes are an ancient cell, appearing in fossilized skeletal remains of early fish and dinosaurs. Despite its relative high abundance, even in the context of nonskeletal cells, the osteocyte is perhaps among the least studied cells in all of vertebrate biology. Osteocytes are cells embedded in bone, able to modify their surrounding extracellular matrix via specialized molecular remodeling mechanisms that are independent of the bone forming osteoblasts and bone-resorbing osteoclasts. Osteocytes communicate with osteoclasts and osteoblasts via distinct signaling molecules that include the RankL/OPG axis and the Sost/Dkk1/Wnt axis, among others. Osteocytes also extend their influence beyond the local bone environment by functioning as an endocrine cell that controls phosphate reabsorption in the kidney, insulin secretion in the pancreas, and skeletal muscle function. These cells are also finely tuned sensors of mechanical stimulation to coordinate with effector cells to adjust bone mass, size, and shape to conform to mechanical demands.


1992 ◽  
Vol 102 (3) ◽  
pp. 643-652 ◽  
Author(s):  
S. Swasdison ◽  
R. Mayne

Two methods were developed in which long-term cultures of quail skeletal muscle were established so that all of the muscle fibers develop in a highly oriented manner. The muscle fibers became spontaneously and vigorously contractile and established strong connections with the extracellular matrix at their ends that closely duplicate the structure of the myotendinous junction. A continuous basal lamina was formed around each muscle fiber that contained type IV collagen, laminin and heparan sulfate proteoglycan. With one of the methods, an extensive extracellular matrix developed around each muscle fiber that was highly organized with the formation of a distinctive epimysium, perimysium and endomysium. Analysis of the cultures by both methods for different isoforms of myosin showed expression of an adult form of myosin by some of the muscle cells. The results therefore demonstrate that muscle development in the present culture systems proceeds extensively for several weeks. It will now be possible to investigate directly the structure of the connections between muscle fibers and the extracellular matrix.


2008 ◽  
Vol 102 (3) ◽  
pp. 372-379 ◽  
Author(s):  
Denise C. Hocking ◽  
Patricia A. Titus ◽  
Ronen Sumagin ◽  
Ingrid H. Sarelius

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