**2.1. Fibril forming collagen types in skeletal muscle**

Type I and III collagen are the most abundant fibril forming collagens in the skeletal muscle. Type I collagen dominates in the intramuscular collagen content – reported from 30% up to 90% of total collagen [10,12]. The epimysium consists mainly of type I collagen with minor amounts of type III collagen [9–11]. Equal amounts of both collagen types are found in the perimysium. In the endomysium, type III collagen is the predominant form and only small amounts of type I collagen are found [2,11]. The smaller average diameter of oxidative muscle fibres should result in a higher endomysial connective tissue content in slow-twitch muscles, as the surface area/volume ratio of each fibre is greater than the average glycolytic fibre in fasttwitch muscle [3]. Slow muscles contain more type I collagen than type III collagen, the proportion of type III collagen is greater in fast muscles [13].

Type I collagen is the major stress-tolerant fibrillar collagen in the muscle. It has a high tensile strength and limited elasticity and is thus well-suited for force transmission [1,2]. Type III collagen, the other main fibrillar collagen, has a structure and arrangement similar to that of type I collagen, but it forms thinner and more elastic fibres. The fibres of type III collagen can also form copolymers with those of type I collagen [7]. Collagens I and III are fibril forming and serve as a supportive structure in the muscle tissue. They attach myocytes and muscle bundles to each other [1,2,11]. Also nerves and capillaries are surrounded and attached to muscle by collagen [11]. Type V collagen is also fibril forming and can be found in the endoand perimysium in smaller amounts than the collagen types I and III [2,10]. Collagens III and V are known to copolymerize with type I collagen and they may have a role in collagen fibre diameter regulation [6,10]. Type V collagen is considered to form the core of the fibrils, and collagens I and III copolymerize around this core [2,3]. Type II and XI collagens are also fibril forming and have been detected in the skeletal muscle only at mRNA level [3,10]. Type V and XI collagens form heterotypic molecules and can be considered as a single kind of collagen [2, 10]. Fibril associated collagens with interrupted helix (FACIT) types XII and XIV are located only in the perimysium [2,14]. These FACIT collagens associate with the surface of interstitial collagen fibrils and possibly act as molecular bridges among or between fibrils and other components of the ECM [2,9]. Although mRNAs of the other members of FACIT subfamily (IX, XVI, XIX, XXI) are detected in the skeletal muscle, the respective proteins have not been found [14,15]. The formation process of fibrillar collagen is depicted on **Figure 1**.

**Figure 1.** The formation process of fibrillar collagen.

It is important to accept that both the tendon and the intramuscular connective tissue interact closely with the contractile elements of the skeletal muscle to transmit force [5–7]. The force transmission from the muscle fibres is not only transformed to the tendon and the subsequent bone via the myotendinous junctions, but also via the lateral transmission between neigh‐ bouring fibres and fascicles within the muscle [1,6]. The tension developed in one part of the muscle can be transmitted via shear links to other parts of the muscle. The perimysium is

The extracellular matrix (ECM) is formed by complex molecular networks, which determine the architecture of a tissue and regulate various biological processes [6,8]. The skeletal muscle ECM is organized in three levels: the epimysium surrounds the entire skeletal muscle, the perimysium surrounds muscle bundles consisting of a variable number of muscle cells, and the endomysium outlines the individual muscle fibres [2,7]. The ECM consists of various substances, of which collagen fibrils and proteoglycans are the most widespread [3,9]. The most abundant protein of the extracellular matrix is collagen, accounting for 20–25% of all protein in the whole body and forming more than 90% of the organic mass of bone [2,6]. At present, 26 different collagen types have been identified [2,10]. Although the impact is not well established, various isoforms of collagen exist, and they have varying strength and functional characteristics [6]. Muscular flexibility is partly provided by collagen. For this purpose the organization of fibrils and fibres is critical, because individual collagen molecules, fibrils, and fibres are intrinsically inextensible [2,11]. The extensibility of collagen results from the straightening of curved fibrils and fibres [2]. In addition to the proteoglycans, the hydrophilic

Type I and III collagen are the most abundant fibril forming collagens in the skeletal muscle. Type I collagen dominates in the intramuscular collagen content – reported from 30% up to 90% of total collagen [10,12]. The epimysium consists mainly of type I collagen with minor amounts of type III collagen [9–11]. Equal amounts of both collagen types are found in the perimysium. In the endomysium, type III collagen is the predominant form and only small amounts of type I collagen are found [2,11]. The smaller average diameter of oxidative muscle fibres should result in a higher endomysial connective tissue content in slow-twitch muscles, as the surface area/volume ratio of each fibre is greater than the average glycolytic fibre in fasttwitch muscle [3]. Slow muscles contain more type I collagen than type III collagen, the

Type I collagen is the major stress-tolerant fibrillar collagen in the muscle. It has a high tensile strength and limited elasticity and is thus well-suited for force transmission [1,2]. Type III collagen, the other main fibrillar collagen, has a structure and arrangement similar to that of type I collagen, but it forms thinner and more elastic fibres. The fibres of type III collagen can also form copolymers with those of type I collagen [7]. Collagens I and III are fibril forming

ECM includes several other proteins such as noncollagen glycoproteins [9].

**2. Functions and composition of ECM in skeletal muscle**

**2.1. Fibril forming collagen types in skeletal muscle**

proportion of type III collagen is greater in fast muscles [13].

especially capable of transmitting tensile force [3,7].

46 Composition and Function of the Extracellular Matrix in the Human Body

#### **2.2. Nonfibrillar collagen types of skeletal muscle.**

Nonfibrillar collagens of the skeletal muscle are mainly located in the basement membranes. The basement membrane (BM) is a highly specialized sheet of the connective tissue surround‐ ing individual muscle fibres, blood vessels, Schwann's cells and the spindle capsule cells. The components of the BM are the regulators of many biological activities such as cell growth, differentiation and migration which influence tissue development and repair [2,6,16]. Integrins attach muscle cells to ECM and serve as the force-transmitters between ECM and the con‐ tracting components inside the muscle cells. They connect laminin to the cell membrane to form the inner layer of basement membrane [3,17].

Type IV collagen is a major component in the basement membrane and therefore plays a critical role in the cellular arrangement in the muscle tissue. It is an integral component of basement membrane and forms a covalently stabilized polymer network around the muscle fibres [2,10]. Type IV collagen molecules form a mesh-like structure outside the laminin layer and give stability to the BM [18]. Laminin and type IV collagen are connected to each other by nidogen-1 in the muscular basement membranes [2,19]. As a part of the flexible basement membrane, type IV collagen network is interconnected with other extracellular matrix compounds and sarcolemmal proteins, being consequently exposed to stretching effects during muscle contraction [20,21]. The formation process of type IV collagen is demonstrated in **Figure 2**.

**Figure 2.** The formation process of type IV collagen.

Type VI collagen interacts with type IV and type I collagens [2,10], providing a link between the basement membranes and the surrounding matrix. Collagens XV and XVII belong to the multiplexin subfamily of nonfibrillar collagens [16] and are located in the basement membrane zone [2,10,16]. Collagens XV and XVIII may have a role in stabilizing the muscle cells [2,10]. Type XIII collagen is the transmembrane protein which is capable of binding certain basement membrane proteins [2,22]. It probably provides a link between the muscle cell and its basement membrane [10]. Type XIII collagen is concentrated in the myotendinous junctions [10,22].
