The Structure and Role of Intramuscular Connective Tissue in Muscle Function

Abstract

Extracellular matrix (ECM) structures within skeletal muscle play an important, but under-appreciated, role in muscle development, function and adaptation. Each individual muscle is surrounded by epimysial connective tissue and within the muscle there are two distinct extracellular matrix (ECM) structures, the perimysium and endomysium. Together, these three ECM structures make up the intramuscular connective tissue (IMCT). There are large variations in the amount and composition of IMCT between functionally different muscles. Although IMCT acts as a scaffold for muscle fiber development and growth and acts as a carrier for blood vessels and nerves to the muscle cells, the variability in IMCT between different muscles points to a role in the variations in active and passive mechanical properties of muscles. Some traditional measures of the contribution of endomysial IMCT to passive muscle elasticity relied upon tensile measurements on single fiber preparations. These types of measurements may now be thought to be missing the important point that endomysial IMCT networks within a muscle fascicle coordinate forces and displacements between adjacent muscle cells by shear and that active contractile forces can be transmitted by this route (myofascial force transmission). The amount and geometry of the perimysial ECM network separating muscle fascicles varies more between different muscle than does the amount of endomysium. While there is some evidence for myofascial force transmission between fascicles via the perimysium, the variations in this ECM network appears to be linked to the amount of shear displacements between fascicles that must necessarily occur when the whole muscle contracts and changes shape. Fast growth of muscle by fiber hypertrophy is not always associated with a high turnover of ECM components, but slower rates of growth and muscle wasting may be associated with IMCT remodeling. A hypothesis arising from this observation is that the level of cell signaling via shear between integrin and dystroglycan linkages on the surface of the muscle cells and the overlying endomysium may be the controlling factor for IMCT turnover, although this idea is yet to be tested.

Keywords: collagen; endomysium; extracellular matrix; intramuscular connective tissue; mechanotransduction; muscle; perimysium.

FIGURE 1

The general structure of intramuscular connective tissue. (A) Schematic diagram showing the general arrangement of the epimysium, perimysium, and endomysium within muscle. (B) Schematic diagram depicting the sparse junction zones between the thick perimysium and the endomysium of muscle fibers in the surface layer of the fascicle. (C) Schematic diagram showing myofibrils of an individual muscle cell residing in the honeycomb network of the endomysium. (D) Low magnification scanning electron micrograph of IMCT structures in muscle after treatment with NaOH to remove myofibrillar proteins and proteoglycans. The thicker perimysium is seen surrounding the honeycombed endomysial network within a fascicle. (E) A higher magnification view of the endomysial network after NaOH treatment. From Purslow (2014), with permission. Panels (D,E) from Purslow and Trotter (1994), with permission.

FIGURE 2

Micrographs of large transverse sections of three muscles from the same (bovine) animal, showing differences in the division of muscles into fascicles by perimysium. Top panel: pectoralis profundus; middle panel: sternocephalicus; bottom panel: rhomboideus cervicus. Differences in fascicle shape, size, and perimysial thickness can be seen between muscles and within each muscle. White gaps visible between fascicles are shrinkage artifacts (separating perimysium from the endomysium of surface muscle fibers) produced by fixation. Adapted from Purslow (2005).

FIGURE 3

Perimysium excised form bovine semitendinosus muscle 24 h post-mortem (A) upstretched and (B) stretched transverse to the muscle fiber direction, with the resulting load-deformation curve shown in (C). In (D) measurements of the angle between the collagen fiber bundles and the stretching direction (triangles) are a reasonable fit to a model sf strain-induced reorientation (Purslow, 1989; fitted line) in the perimysium. Reproduced from Purslow (1999).

FIGURE 4

Three muscle fibers dissected post-rigor from rat gastrocnemius muscle forming a Y-shaped specimen suitable for measuring the shear properties of endomysium. Bottom: schematic representation. Middle panel: polarized light micrograph of the whole preparation. Top panel: higher-magnification phase contrast image of the mid-section, showing the free ends of the outer two fibers.