The structure and functional significance of variations in the connective tissue within muscle

Abstract

The amount of intramuscular connective tissue (IMCT) and its morphological distribution is highly variable between muscles of differing function. The functional roles of this component of muscle have been poorly understood, but a picture is gradually emerging of the central role this component has in growth, transmission of mechanical signals to muscle cells and co-ordination of forces between fibres within a muscle. The aim of this review is to highlight recent advances that begin to show the functional significance of some of the variability in IMCT. IMCT has a number of clearly defined roles. It patterns muscle development and innervation, and mechanically integrates the tissue. In developing muscles, proliferation and growth of muscle cells is stimulated and guided by cell–matrix interactions. Recent work has shown that the topography of collagen fibres is an important signal. The timing and rates of expression of connective tissue proteins also show differences between muscles. Discussion of mechanical roles for IMCT has traditionally been limited to the passive elastic response of muscle. However, it is now clear that IMCT provides a matrix to integrate the contractile function of the whole tissue. Mechanical forces are co-ordinated and passed between adjacent muscle cells via cell–matrix interactions and the endomysial connective tissue that links the cells together. An emerging concept is that division of a muscle into fascicles by the perimysial connective tissue is related to the need to accommodate shear strains as muscles change shape during contraction and extension.

Introduction

Perhaps one of the most striking and easily visualised variations between muscles upon dissection is the pattern of their internal organisation into fascicles and fibres by intramuscular connective tissue (IMCT). The general structure, morphology and composition of IMCT has previously been reviewed (Mayne and Sanderson, 1985, Purslow and Duance, 1990, McCormick, 1994) and will not be repeated in detail here. In essence, individual muscles are encased by the epimysium, fascicles within the muscle are delineated by the perimysium, and individual muscle fibres are separated by the endomysium, as shown schematically in Fig. 1. All three IMCT structures (epimysium, perimysium and endomysium) generally differ in composition and structure, as previously reviewed (Purslow and Duance, 1990). More recent work (Listrat et al., 1999, Listrat et al., 2000) has increased the number of collagen types identified in IMCT to seven (types I, III, IV, V, VI, XII and XIV). Whilst it is now appreciated that the content of type V collagen in the major IMCT structure of fish muscle, the myocommata, is higher than that of mammalian muscle (Sato et al., 1998), no clear picture of the significance of these compositional variations has emerged; types I and III are still considered the major fibrous collagen species in the epimysium, perimysium and reticular layer of the endomysium, with collagen type IV making up the basement membrane immediately outside the sarcolemmal plasma membrane. The precise role of the minor collagen components remains somewhat obscure, but regulation of collagen fibre diameter is a strong possibility.

Proteoglycans (PGs) play an important and increasingly recognised role in linking together the fibrous elements of the extracellular matrix (Scott, 1980, Scott, 1990). In terms of IMCT, there has been growing recognition of the functional importance and composition of proteoglycans in the last 10 years. Previous findings (Carrino and Caplan, 1982, Carrino and Caplan, 1984, Anderson et al., 1984) on the association of heparan sulfate-containing PGs with the basement membrane and high concentrations of chondroitin sulfate in the perimysium were confirmed by Nishimura et al. (1996), who identified PGs associated with the basement membrane and endomysium in bovine semitendinosus as principally containing heparan sulfates, whilst those in the perimysium were rich in chondroitin and dermatan sulfate. Nakano et al. (1997) reported intense immunolabelling for decorin, together with weaker chondroitin sulfate labelling in bovine IMCT. Eggen et al. (1994) also showed decorin to be a component in the IMCT of bovine muscle. Decorin is known to interact with collagen in the extracellular matrix. Nishimura et al. (1997) reported that decorin is only visible by immunohistochemical labelling postnatally in the semitendinosus muscle of calves and that chondroitin sulfate labelling of PGs in the perimysium increases progressively during postnatal development. Conversely, Velleman et al. (1999) reported chondroitin sulfate-containing PGs to be dominant in early stages of turkey pectoralis muscle, with heparan sulfate levels increasing in late embryonic term. Whether the differences between these two studies are due to species or muscle differences is not known, but a systematic investigation of PGs in various muscles from one species would seem valuable.

The general features summarised above describe the IMCT in a wide range of muscles. Systematic differences in morphological distribution, amounts and composition of IMCT can be observed between muscles of different maturity or from different parts of the body. It is generally accepted that these differences reflect some differences in the functional properties of the muscle, so that these variations in IMCT represent some functional fine-tuning. In order to assess the validity of this hypothesis, we must first ask what the roles of IMCT actually are and assess whether the patterns of variability of structure and composition of IMCT are compatible with variations in these roles. Careful comparison of these may suggest the relative importance of differing functions of the IMCT.