From the Greek for glue, kolla, the word collagen means "glue producer" and refers to the early process of boiling the skin and sinews of horses and other animals to obtain glue. Collagen adhesive was used by Egyptians about 4,000 years ago, and Native Americans used it in bows about 1,500 years ago. The oldest glue in the world, carbon-dated as more than 8,000 years old, was found to be collagen—used as a protective lining on rope baskets and embroidered fabrics, and to hold utensils together; also in crisscross decorations on human skulls. Collagen normally converts to gelatin, but survived due to the dry conditions. Animal glues are thermoplastic, softening again upon reheating, and so they are still used in making musical instruments such as fine violins and guitars, which may have to be reopened for repairs—an application incompatible with tough, synthetic plastic adhesives, which are permanent. Animal sinews and skins, including leather, have been used to make useful articles for millennia.
Collagens are widely employed in the construction of artificial skin substitutes used in the management of severe burns. These collagens may be derived from bovine, equine or porcine, and even human, sources and are sometimes used in combination with silicones, glycosaminoglycans, fibroblasts, growth factors and other substances.
Collagen is also sold commercially as a joint mobility supplement. This lacks supportive research as the proteins would just be broken down into its base amino acids during digestion, and could go to a variety of places besides the joints depending upon need and DNA orders.
Recently an alternative to animal-derived collagen has become available. Although expensive, this human collagen, derived from donor cadavers, placentas and aborted fetuses, may minimize the possibility of immune reactions.
Collagen is now being used as a main ingredient for some cosmetic makeup.
A distinctive feature of collagen is the regular arrangement of amino acids in each of the three chains of these collagen subunits. The sequence often follows the pattern Gly-Pro-Y or Gly-X-Hyp, where X and Y may be any of various other amino acid residues. Proline or hydroxyproline constitute about 1/6 of the total sequence. With Glycine accounting for the 1/3 of the sequence, this means that approximately half of the collagen sequence is not glycine or proline, a fact often missed due to the distraction of the unusual GXY character of collagen alpha-peptides. This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk fibroin. 75-80% of silk is (approximately) -Gly-Ala-Gly-Ala- with 10% serine—and elastin is rich in glycine, proline, and alanine (Ala), whose side group is a small, inert methyl group. Such high glycine and regular repetitions are never found in globular proteins save for very short sections of their sequence. Chemically-reactive side groups are not needed in structural proteins as they are in enzymes and transport proteins, however collagen is not quite just a structural protein. Due to its key role in the determination of cell phenotype, cell adhesion, tissue regulation and infrastructure, many sections of its non-proline rich regions have cell or matrix association / regulation roles. The relatively high content of Proline and Hydroxyproline rings, with their geometrically constrained carboxyl and (secondary) amino groups, along with the rich abundance of glycine, accounts for the tendency of the individual polypeptide strands to form left-handed helices spontaneously, without any intrachain hydrogen bonding.
Because glycine is the smallest amino acid with no side-chain, it plays a unique role in fibrous structural proteins. In collagen, Gly is required at every third position because the assembly of the triple helix puts this residue at the interior (axis) of the helix, where there is no space for a larger side group than glycine’s single hydrogen atom. For the same reason, the rings of the Pro and Hyp must point outward. These two amino acids help stabilize the triple helix—Hyp even more so than Pro—a lower concentration of them is required in animals such as fish, whose body temperatures are lower then most warm-blooded animals.
The tropocollagen subunits spontaneously self-assemble, with regularly staggered ends, into even larger arrays in the extracellular spaces of tissues. In the fibrillar collagens, the molecules are staggered from each other by about 67nm (a unit that is referred to as ‘D’ and changes depending upon the hydration state of the aggregate). Each D-period contains 4 and a fraction collagen molecules. This is because 300 nm divided by 67 nm does not give an integer (the length of the collagen molecule divided by the stagger distance D). Therefore in each D-period repeat of the microfibril, there is a part containing 5 molecules in cross-section – called the “overlap” and a part containing only 4 molecules. The triple-helices are also arranged in a hexagonal or quasi-hexagonal array in cross-section, in both the gap and overlap regions.
There is some covalent crosslinking within the triple helices, and a variable amount of covalent crosslinking between tropocollagen helices forming well organized aggregates (such as fibrils). Larger fibrillar bundles are formed with the aid of several different classes of proteins (including different collagen types), glycoproteins and proteoglycans to form the different types of mature tissues from alternate combinations of the same key players. Collagen's insolubility was a barrier to the study of monomeric collagen until it was found that tropocollagen from young animals can be extracted because it is not yet fully crosslinked. However, advances in microscopy techniques (Electron Microscopy - EM and Atomic Force Microscopy -AFM) and X-ray diffraction have enabled researchers to obtain increasingly detailed images of collagen structure in situ. These later advances are particularly important to better understanding the way in which collagen structure affects cell-cell and cell-matrix communication and how tissues are constructed in growth and repair, and changed in development and disease.
Collagen fibrils are collagen molecules packed into an organized overlapping bundle. Collagen fibers are bundles of fibrils.
Collagen fibrils / aggregates are arranged in different combinations and concentrations in various tissues to provide varying tissue properties. In bone, entire collagen triple helices lie in a parallel, staggered array. 40 nm gaps between the ends of the tropocollagen subunits probably serve as nucleation sites for the deposition of long, hard, fine crystals of the mineral component, which is (approximately) hydroxyapatite, Ca10(PO4)6 (OH)2with some phosphate. It is in this way that certain kinds of cartilage turn into bone. Type I collagen gives bone its tensile strength.
Collagen diseases commonly arise from genetic defects that affect the biosynthesis, assembly, postranslational modification, secretion, or other processes in the normal production of collagen.
|I||This is the most abundant collagen of the human body. It is present in scar tissue, the end product when tissue heals by repair. It is found in tendons, skin, artery walls, the endomysium of myofibrils, fibrocartilage, and the organic part of bones and teeth.||COL1A1, COL1A2||osteogenesis imperfecta, Ehlers-Danlos Syndrome|
|II||Hyaline cartilage, makes up 50% of all cartilage protein. Vitreous humour of the eye. Fibrocartilage.||COL2A1||Collagenopathy, types II and XI|
|III||This is the collagen of granulation tissue, and is produced quickly by young fibroblasts before the tougher type I collagen is synthesized. Reticular fiber. Also found in artery walls, skin, intestines and the uterus||COL3A1||Ehlers-Danlos Syndrome|
|IV||basal lamina; eye lens. Also serves as part of the filtration system in capillaries and the glomeruli of nephron in the kidney.||COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6||Alport syndrome|
|V||most interstitial tissue, assoc. with type I, associated with placenta||COL5A1, COL5A2, COL5A3||Ehlers-Danlos syndrome (Classical)|
|VI||most interstitial tissue, assoc. with type I||COL6A1, COL6A2, COL6A3||Ulrich myopathy and Bethlem myopathy|
|VII||forms anchoring fibrils in dermal epidermal junctions||COL7A1||epidermolysis bullosa|
|VIII||some endothelial cells||COL8A1, COL8A2||-|
|IX||FACIT collagen, cartilage, assoc. with type II and XI fibrils||COL9A1, COL9A2, COL9A3||- EDM2 and EDM3|
|X||hypertrophic and mineralizing cartilage||COL10A1||-|
|XI||cartilage||COL11A1, COL11A2||Collagenopathy, types II and XI|
|XII||FACIT collagen, interacts with type I containing fibrils, decorin and glycosaminoglycans||COL12A1||-|
|XIII||transmembrane collagen, interacts with integrin a1b1, fibronectin and components of basement membranes like nidogen and perlecan.||COL13A1||-|
|XVII||transmembrane collagen, also known as BP180, a 180 kDa protein||COL17A1||Bullous Pemphigoid and certain forms of junctional epidermolysis bullosa|
|XVIII||source of endostatin||COL18A1||-|
|XXIII||MACIT collagen -||COL23A1||-|
|XXIX||epidermal collagen||COL29A1||Atopic Dermatitis|
In addition to the above mentioned disorders, excessive deposition of collagen occurs in Scleroderma.
The best stain for use in differentiating collagen from other fibers is Masson's trichrome stain.
Many bacteria and viruses have virulence factors which destroy collagen or interfere with its production.
Julian Voss-Andreae has created sculptures based on the collagen structure out of bamboo and stainless steel. His piece "Unraveling Collagen" is, according to the artist, a "metaphor for aging and growth.