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Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals, making up about 25% of the total protein content.
It is one of the long, fibrous structural proteins whose functions are quite different from those of globular proteins such as enzymes; tough bundles of collagen called collagen fibers are a major component of the extracellular matrix that supports most tissues and gives cells structure from the outside, but collagen is also found inside certain cells. Collagen has great tensile strength, and is the main component of fascia, cartilage, ligaments, tendons, bone and teeth. Along with soft keratin, it is responsible for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging. It strengthens blood vessels and plays a role in tissue development. It is present in the cornea and lens of the eye in crystalline form. It is also used in cosmetic surgery and burns surgery.
If collagen is partially hydrolyzed, the three tropocollagen strands separate into globular, random coils, producing gelatin, which is used in many foods, including flavored gelatin desserts. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries.[1] Nutritionally, collagen and gelatin are poor quality protein because even if sometimes complete protein, are lacking adequate amounts of some of the 8 essential amino acids. Some selling collagen-based dietary supplements claim they improve skin and fingernail quality and aid joint health, but no mainstream scientific research supports these claims. Such loss of health is more likely to be due to things beside protein deficiency, and if it were due to that, other protein sources are better suited for dealing with shortages. Gelatin is still a good source of bulk protein in the diet however, and taking an amino acid blend directly related to the tissue saves the time of manufacturing higher-order amino acids from the baser 8 essential ones.
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.[2] 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.
Gelatin-resorcinol-formaldehyde glue (and with formaldehyde replaced by less-toxic pentanedial and ethanedial) has been used to repair experimental incisions in rabbit lungs.[3]
Collagen has been widely used in cosmetic surgery, as a healing aid for burn patients for reconstruction of bone and a wide variety of dental, orthopedic and surgical purposes. Some points of interest are:
Collagens are widely employed in the construction of artificial skin substitutes used in the management of severe burns, as well as for a wide range of dental, orthopedic, and surgical purposes. 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 recombinant human collagen, derived from donor cadavers and aborted fetuses,[4] may minimize the possibility of immune reactions and other risks.
The tropocollagen or "collagen molecule" subunit is a rod about 300 nm long and 1.5 nm in diameter, made up of three polypeptide strands, each of which is a left-handed helix, not to be confused with the commonly occurring alpha helix, which is right-handed. These three left-handed helices are twisted together into a right-handed coiled coil, a triple helix, a cooperative quaternary structure stabilized by numerous hydrogen bonds. Tropocollagen subunits spontaneously self-assemble, with regularly staggered ends, into even larger arrays in the extracellular spaces of tissues. There is some covalent crosslinking within the triple helices, and a variable amount of covalent crosslinking between tropocollagen helices, to form the different types of collagen found in different mature tissues — similar to the situation found with the α-keratins in hair. Collagen's insolubility was a barrier to study until it was found that tropocollagen from young animals can be extracted because it is not yet fully crosslinked.
Collagen fibrils are collagen molecules packed into an organized overlapping bundle. Collagen fibers are bundles of fibrils.
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-X-Pro or Gly-X-Hyp, where X may be any of various other amino acid residues. Gly-Pro-Hyp occurs frequently. 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. Such high glycine and regular repetitions are never found in globular proteins. Chemically-reactive side groups are not needed in structural proteins as they are in enzymes and transport proteins. The high content of Pro and Hyp rings, with their geometrically constrained carboxyl and (secondary) amino groups, 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, 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 thermally stabilize the triple helix — Hyp even more so than Pro — and less of them is required in animals such as fish, whose body temperatures are low.
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, Ca<sub>5</sub>(PO<sub>4</sub>)<sub>3</sub>(OH), with some phosphate. It is in this way that certain kinds of cartilage turn into bone. Collagen gives bone its elasticity and contributes to fracture resistance.
Collagen occurs in many places throughout the body. There are 28 types of collagen described in literature.
Collagen diseases commonly arise from genetic defects that affect the biosynthesis, assembly, postranslational modification, secretion, or other processes in the normal production of collagen.
In histology, collagen is brightly eosinophilic (pink) in standard H&E slides. The dye methyl violet may be used to stain the collagen in tissue samples.
The dye methyl blue can also be used to stain collagen and immunohistochemical stains are available if required.
The best stain for use in differentiating collagen from other fibers is Masson's trichrome stain.
Collagen is birefringent when stained with Sirius red F3B (C.I. 35782). [5]
Collagen has an unusual amino acid composition and sequence:
Most collagen forms in a similar manner, but the following process is typical for type I:
Vitamin C deficiency causes scurvy, a serious and painful disease in which defective collagen prevents the formation of strong connective tissue. Gums deteriorate and bleed, with loss of teeth; skin discolors, and wounds do not heal. Prior to the eighteenth century, this condition was notorious among long duration military, particularly naval, expeditions during which participants were deprived of foods containing Vitamin C. In the human body, a malfunction of the immune system, called an autoimmune disease, results in an immune response in which healthy collagen fibers are systematically destroyed with inflammation of surrounding tissues. The resulting disease processes are called Lupus erythematosus, and rheumatoid arthritis, or collagen tissue disorders.[6]
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"[7][8].
<gallery> Image:Collagen.gif|Collagen Image:Action de la lysyl oxydase.jpg|Action of lysyl oxydase (in French) </gallery>