Comparative Biochemistry and Physiology Part A 133 (2002) 947–966 1095-6433/02/$ - see front matter  2002 Elsevier Science Inc. All rights reserved. PII: S1095-6433 Ž 02 . 00141-1 The structure and functional significance of variations in the connective tissue within muscle  Peter P. Purslow* Department of Biological Sciences, University of Stirling, Stirling FK9 4LA, Scotland, UK Received 9 January 2002; received in revised form 30 April 2002; accepted 1 May 2002 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.  2002 Elsevier Science Inc. All rights reserved. Keywords: Extracellular matrix; Muscle; Connective tissue; Collagen; Growth; Mechanical properties; Cell signalling; Mechanotransduction 1. Introduction Perhaps one of the most striking and easily visualised variations between muscles upon dissec- tion is the pattern of their internal organisation into fascicles and fibres by intramuscular connec- tive tissue (IMCT). The general structure, mor- phology and composition of IMCT has previously  This paper was presented at ‘Tendon – Bridging the Gap’, a symposium at the 2002 Society of Integrative and Compar- ative Biology. Participation was funded by SICB, The Shriners Hospitals for Children, and the National Science Foundation (IBN-0127260). *Tel.: q44-1786-467783; fax: q44-1786-464994. E-mail address: p.p.purslow@stir.ac.uk (P.P. Purslow). been reviewed (Mayne and Sanderson, 1985; Pur- slow 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 sep- arated 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, 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