Collagen is most abundant in animal tissues as very long fibrils with a characteristic axial periodic structure. The fibrils provide the major biomechanical scaffold for cell attachment and anchorage of macromolecules, allowing the shape and form of tissues to be defined and maintained. How the fibrils are formed from their monomeric precursors is the primary concern of this review. Collagen fibril formation is basically a self-assembly process (i.e. one which is to a large extent determined by the intrinsic properties of the collagen molecules themselves) but it is also sensitive to cell-mediated regulation, particularly in young or healing tissues. Recent attention has been focused on "early fibrils' or "fibril segments' of approximately 10 microns in length which appear to be intermediates in the formation of mature fibrils that can grow to be hundreds of micrometers in length. Data from several laboratories indicate that these early fibrils can be unipolar (with all molecules pointing in the same direction) or bipolar (in which the orientation of collagen molecules reverses at a single location along the fibril). The occurrence of such early fibrils has major implications for tissue morphogenesis and repair. In this article we review the current understanding of the origin of unipolar and bipolar fibrils, and how mature fibrils are assembled from early fibrils. We include preliminary evidence from invertebrates which suggests that the principles for bipolar fibril assembly were established at least 500 million years ago.

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In the series-fibred muscle architecture commonly found in large muscles of mammals and birds, the intrafasciculary-terminating muscle fibres have no direct tendinous attachments. Contractile force produced in these fibres must be transmitted between adjacent muscle fibres via the endomysial connective tissue which separates them. The endomysium is thus an essential mechanical component in such muscles. Studies of motor end-plate banding patterns and the frequent occurrence of tapering ends of fibres within the fascicles of the bovine sternomandibularis muscle show it to be a series-fibred muscle. Sodium hydroxide digestion of fixed samples of this muscle to remove the myofibrillar apparatus revealed the endomysium to be a disordered planar network of mainly curvilinear collagen fibrils. The orientation distribution of the collagen fibrils in the endomysial network was measured by image analysis of scanning electron micrographs. Analysis of endomysial preparations from muscle fixed at sarcomere lengths between 1-4 microns showed that the orientation distribution of collagen fibrils is quantitatively related to muscle length. At rest sarcomere length the collagen fibril network is not completely random, but has a slight circumferential bias. The orientation distribution shows a progressive shift towards the circumferential direction at short sarcomere lengths and towards the longitudinal direction at long sarcomere lengths. The relationship between the number-weighted mean collagen orientation and sarcomere length was compared to two geometric models of network behaviour, the isoareal and constant shape models. Both fitted the data reasonably, although the constant shape model described the rate of change of mean orientation more closely. From fibrous composites theory, the reinforcement efficiency factor, eta, was calculated from the measured collagen fibril orientation distributions. These calculations predict a non-linearly increasing longitudinal tensile modulus for the endomysium with increasing sarcomere length, in agreement with its known non-linear properties, but confirm that the tensile properties of the endomysium are unsuitable for transmission of tensile force from muscle fibres contracting near rest length. This reinforces a previous interpretation that contractile force is transmitted between neighbouring muscle fibres by trans-laminar shear through the endomysium rather than by in-plane tension.

Many skeletal muscles, including the feline biceps femoris, are composed of short, tapered myofibers arranged in an overlapping longitudinal series. The endomysium of such muscles transfers tension between overlapping myofibers, and is thus an elastic element in series with them. The endomysium of the cat biceps femoris contains curvilinear collagen fibrils in an approximately isotropic (random) array. The collagen fibrils undergo only a modest reorientation as the myofibers shorten or lengthen within the physiological range. A geometrical model predicts no change in the thickness of the endomysium on changing muscle fiber length and quantifies the expected collagen fibril reorientation in the endomysium as a function of muscle extension. It is also demonstrated that a high proportion of the collagen fibrils will be curvilinear at all sarcomere lengths. The organization of endomysial collagen is appropriate for the transfer of loads between myofibers by means of shear.

The work done by the contractile proteins of muscle in accelerating, decelerating, or maintaining the positions of skeletal elements requires the efficient transmission of tension across the surface membranes of the fibers. The most widely studied sites of tension transmission are the ends of muscle fibers where they contact either connective or epithelial tissues. In most animals, regardless of phylum, muscle fiber ends are characteristically folded, producing a junctional interface that significantly reduces the absolute value of stress applied to the cell membrane, insures that the principle stress vector at the cell membrane is shear rather than tension, and minimizes stress concentrations. The morphological and molecular similarities of muscle-tendon junctions (MTJs) in different animals suggest that the problem of creating a strong adhesive joint between a muscle fiber and a tissue of dissimilar physical properties is essentially the same for all muscles, and that the solution arose early in evolution. In addition to those muscle fiber ends that occur where fibers contact dissimilar tissues, there are intramuscular fiber terminations that consist either of folded cell-cell junctions similar to the fasciae adherentes of cardiac muscle, or of gradually tapering fiber ends. Both sorts of intramuscular ends occur in those vertebrate muscles in which the individual muscle fibers are too short to reach from the tendon of origin to the tendon of insertion. In series-fibered muscles in which the fiber ends are tapered, tension is transmitted from contractile proteins to endomysial collagen fibrils across the fiber membranes. The endomysium of such muscles is an essential series-elastic element. The existing evidence suggests that tension transmission is a general property of muscle cell surfaces, and that specific junctional morphologies are the results of dynamic interactions between muscle cells and the tissues to which they adhere.