Basic Structure, Physiology, and Biochemistry of Connective Tissues and Extracellular Matrix Collagens

Adv Exp Med Biol. 2021:1348:5-43. doi: 10.1007/978-3-030-80614-9_2.


The physiology of connective tissues like tendons and ligaments is highly dependent upon the collagens and other such extracellular matrix molecules hierarchically organized within the tissues. By dry weight, connective tissues are mostly composed of fibrillar collagens. However, several other forms of collagens play essential roles in the regulation of fibrillar collagen organization and assembly, in the establishment of basement membrane networks that provide support for vasculature for connective tissues, and in the formation of extensive filamentous networks that allow for cell-extracellular matrix interactions as well as maintain connective tissue integrity. The structures and functions of these collagens are discussed in this chapter. Furthermore, collagen synthesis is a multi-step process that includes gene transcription, translation, post-translational modifications within the cell, triple helix formation, extracellular secretion, extracellular modifications, and then fibril assembly, fibril modifications, and fiber formation. Each step of collagen synthesis and fibril assembly is highly dependent upon the biochemical structure of the collagen molecules created and how they are modified in the cases of development and maturation. Likewise, when the biochemical structures of collagens or are compromised or these molecules are deficient in the tissues - in developmental diseases, degenerative conditions, or injuries - then the ultimate form and function of the connective tissues are impaired. In this chapter, we also review how biochemistry plays a role in each of the processes involved in collagen synthesis and assembly, and we describe differences seen by anatomical location and region within tendons. Moreover, we discuss how the structures of the molecules, fibrils, and fibers contribute to connective tissue physiology in health, and in pathology with injury and repair.

Keywords: Basement membrane collagen; Beaded filament-forming collagen; Collagen fibril assembly; Collagen in repair; Collagens I-XXVIII; Crosslinking; Enthesis; Fibril-associated collagens with interrupted triple helices (FACIT); Fibril-forming collagens; Hexagonal network-forming collagen; Hierarchical structure of tendon; Ligaments; Mature tendon fibrils; Mechanical behavior; Midsubstance; Procollagens; Protofibrils; Small leucine-rich proteoglycans (SLRPs); Supramolecular structures of collagens; Transmembrane collagens; Triple helix.

MeSH terms

  • Collagen*
  • Connective Tissue
  • Extracellular Matrix*
  • Fibrillar Collagens
  • Tendons


  • Fibrillar Collagens
  • Collagen