Collagen
Tropocollagen triple helix

Collagen /ˈkɒlədʒɨn/ is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals.[1] It is the main component of connective tissue, and is the most abundant protein in mammals,[2] making up about 25% to 35% of the whole-body protein content. Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendon, ligament and skin, and is also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc. The fibroblast is the most common cell which creates collagen.

In muscle tissue, it serves as a major component of the endomysium. Collagen constitutes one to two percent of muscle tissue, and accounts for 6% of the weight of strong, tendinous muscles.[3] Gelatin, which is used in food and industry, is collagen that has been irreversibly hydrolyzed.

Contents

History and background

The molecular and packing structures of collagen have eluded scientists over decades of research. The first evidence that it possesses a regular structure at the molecular level was presented in the mid-1930s.[4][5] Since that time, many prominent scholars, including Nobel laureates Crick, Pauling, Rich and Yonath, and others, including Brodsky, Berman, and Ramachandran, concentrated on the conformation of the collagen monomer. Several competing models, although correctly dealing with the conformation of each individual peptide chain, gave way to the triple-helical "Madras" model, which provided an essentially correct model of the molecule's quaternary structure[6][7][8] although this model still required some refinement.[9][10][11][12] The packing structure of collagen has not been defined to the same degree outside of the fibrillar collagen types, although it has been long known to be hexagonal ...or quasi-hexagonal.[13][14][15] As with its monomeric structure, several conflicting models alleged that either the packing arrangement of collagen molecules is 'sheet-like' or microfibrillar.[16][17] The microfibrillar structure of collagen fibrils in tendon, cornea and cartilage has been directly imaged by electron microscopy.[18][19][20] In 2006, the microfibrillar structure of adult tendon, as described by Fraser, Miller, and Wess (amongst others), was confirmed as being closest to the observed structure, although it oversimplified the topological progression of neighboring collagen molecules, and hence did not predict the correct conformation of the discontinuous D-periodic pentameric arrangement termed simply: the microfibril.[21] Various cross linking agents like dopaquinone, embelin, potassium embelate and 5-O-methyl embelin could be developed as potential cross-linking/stabilization agent of collagen preparation and its application as wound dressing sheet in clinical applications is enhanced.[22]

Chemistry of Collagen

Collagen is a composed of a triple helix, which generally consists of two identical chains (α1) and an additional chain that differs slightly in its chemical composition (α2)[23]. The amino acid composition of collagen is atypical for proteins, particularly with respect to its high hydroxyproline content. The most common motifs in the amino acid sequence of collagen are Glycine-Proline-X and Glycine-X-Hydroxyproline, where X is any amino acid other than glycine, proline or hydroxyproline. The average amino acid composition for fish and mammal skin is given[23].

Amino Acid Abundance in Mammal Skin (Residues/1000) Abundance in Fish Skin (Residues/1000)
Asp 47 47
Hyp 95 67
Thr 19 26
Ser 36 46
Glu 74 76
Pro 126 108
Gly 329 339
Ala 109 114
Val 22 21
Met 6 13
Ile 11 11
Leu 24 23
Tyr 3 3
Phe 13 14
Hyl 6 8
Lys 29 26
His 5 7
Arg 49 52

Synthesis of Collagen

The synthesis of collagen occurs inside and outside of the cell. The formation of collagen which results in fibrillary collagen (most common form) is discussed here. Meshwork collagen, which is often involved in the formation of filtration systems is the other form of collagen. It should be noted that all types of collagens are triple helixes, and the differences lie in the make-up of the alpha peptides created in step 2.

  1. Transcription of mRNA: There are approximately 34 genes associated with collagen formation, each coding for a specific mRNA sequence, and typically have the "COL" prefix. The beginning of collagen synthesis begins with turning on genes which are associated with the formation of a particular alpha peptide (typically alpha 1, 2 or 3).
  2. Pre-pro-peptide Formation: Once the final mRNA exits from the cell nucleus and enters into the cytoplasm it links with the ribosomal subunits and the process of translation occurs. The early/first part of the new peptide is known as the signal sequence. The signal sequence on the N-terminal of the peptide is recognized by a signal recognition particle on the endoplasmic reticulum, which will be responsible for directing the pre-pro-peptide into the endoplasmic reticulum. Therefore, once the synthesis of new peptide is finished, it goes directly into the endoplasmic reticulum for post-translational processing. Note that it is not known as pre-pro-collagen.
  3. Alpha Peptide to Procollagen: Three modifications of the pre-pro-peptide occurs leading to the formation of the alpha peptide. Secondly, the triple helix known as procollagen is formed before being transported in a transport vesicle to the golgi apparatus. 1) The signal peptide on the N-terminal is dissolved, and the molecule is now known as propeptide (not procollagen). 2) Hydroxylation of lysines and prolines on propeptide by the enzymes prolyl hydroxylase and lysyl hydroxylase (to produce hydroxyproline and hydroxylysine) occurs to aid crosslinking of the alpha peptides. It is this enzymatic step that requires vitamin C as a cofactor. In scurvy, the lack of hydroxylation of prolines and lysines causes a looser triple helix (which is formed by 3 alpha peptides). 3) Glycosylation occurs by adding either glucose or galactose monomers onto the hydroxy groups that were placed onto lysines, but not on prolines. From here the hydroxylated and glycosylated propeptide twists towards the left very tightly and then three propeptides will form a triple helix. It is important to remember that this molecule, now known as procollagen (not propeptide) is composed of a twisted portion (center) and two loose ends on either end. At this point the procollagen is packaged into a transfer vesicle destined for the golgi apparatus.
  4. Golgi Apparatus Modification: In the golgi apparatus, the procollagen goes through one last post-translational modification before being secreted out of the cell. In this step oligosaacharides (not monosaacharides like in step 3) are added, and then the alpha peptide is packaged into a secretory vesicle destined for the extracellular space.
  5. Formation of Tropocollagen: Once outside the cell, membrane bound enzymes known as collagen peptidases, remove the "loose ends" of the procollagen molecule. What is left is known as tropocollagen. Defect in this step produces one of the many collagenopathies known as Ehlers-danlos syndrome.This step is absent when synthesizing type IV or meshwork collagen.
  6. Formation of the Collagen Fibril: Lysyl oxidase and extracellular enzyme produces the final step in the collagen synthesis pathway. This enzyme acts on lysines and hydroxylysines producing aldehyde groups, which will eventually undergo covalent bonding between tropocollagen molecules. This polymer of tropocollogen is known as a collagen fibril.

Molecular structure

The tropocollagen or collagen molecule is a subunit of larger collagen aggregates such as fibrils. At approximately 300 nm long and 1.5 nm in diameter, it is made up of three polypeptide strands (called alpha peptides, see step 2), each possessing the conformation of a left-handed helix (its name is not to be confused with the commonly occurring alpha helix, a right-handed structure). These three left-handed helices are twisted together into a right-handed coiled coil, a triple helix or "super helix", a cooperative quaternary structure stabilized by numerous hydrogen bonds. With type I collagen and possibly all fibrillar collagens if not all collagens, each triple-helix associates into a right-handed super-super-coil referred to as the collagen microfibril. Each microfibril is interdigitated with its neighboring microfibrils to a degree that might suggest they are individually unstable, although within collagen fibrils, they are so well ordered as to be crystalline.

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-X or Gly-X-Hyp, where X may be any of various other amino acid residues[23]. Proline or hydroxyproline constitute about 1/6 of the total sequence. With glycine accounting for the 1/3 of the sequence, this means approximately half of the collagen sequence is not glycine, proline or hydroxyproline, a fact often missed due to the distraction of the unusual GX1X2 character of collagen alpha-peptides. The high glycine content of collagen is important with respect to stabilization of the collagen helix as this allows the very close association of the collagen fibers within the molecule, facilitating hydrogen bonding and the formation of intermolecular cross-links[23]. This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk fibroin. About 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 nonproline-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 than most warm-blooded animals. Lower proline and hydroxyproline contents are characteristic of cold-water, but not warm-water fish; the latter tend to have similar proline and hydroxyproline contents to mammals[23]. The lower proline and hydroxproline contents of cold-water fish and other poikilotherm animals leads to their collagen having a lower thermal stability than mammalian collagen[23]. This lower thermal stability means that gelatin derived from fish collagen is not suitable for many Gelatin.

The tropocollagen subunits spontaneously self-assemble, with regularly staggered ends, into even larger arrays in the extracellular spaces of tissues.[24][25] In the fibrillar collagens, the molecules are staggered from each other by about 67 nm (a unit that is referred to as ‘D’ and changes depending upon the hydration state of the aggregate). Each D-period contains four plus a fraction collagen molecules, 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 five molecules in cross-section, called the “overlap”, and a part containing only four molecules, called the "gap".[21] The triple-helices are also arranged in a hexagonal or quasihexagonal array in cross-section, in both the gap and overlap regions.[13][21]

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).[26] 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.[25] 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.[27][28] For example using AFM –based nanoindentation it has been shown that a single collagen fibril is a heterogeneous material along its axial direction with significantly different mechanical properties in its gap and overlap regions, correlating with its different molecular organizations in these two regions.[29]

Collagen fibrils are semicrystalline aggregates of collagen molecules. 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. Forty nm gaps between the ends of the tropocollagen subunits (approximately equal to the gap region) 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)2 with some phosphate. It is in this way that certain kinds of cartilage turn into bone. Type I collagen gives bone its tensile strength.

Types and associated disorders

Collagen occurs in many places throughout the body. Over 90% of the collagen in the body, however, is of type one.[30]

So far, 28 types of collagen have been identified and described. The five most common types are:

  • Collagen I: skin, tendon, vascular ligature, organs, bone (main component of the organic part of bone)
  • Collagen II: cartilage (main component of cartilage)
  • Collagen III: reticulate (main component of reticular fibers), commonly found alongside type I.
  • Collagen IV: forms bases of cell basement membrane
  • Collagen V: cells surfaces, hair and placenta

Collagen-related diseases most commonly arise from genetic defects or nutritional deficiencies that affect the biosynthesis, assembly, postranslational modification, secretion, or other processes involved in normal collagen production.

Type Notes Gene(s) Disorders
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, Infantile cortical hyperostosis aka Caffey's disease
II Hyaline cartilage, makes up 50% of all cartilage protein. Vitreous humour of the eye. 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, Dupuytren's contracture
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, Goodpasture's 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 dystrophica
VIII some endothelial cells COL8A1, COL8A2 Posterior polymorphous corneal dystrophy 2
IX FACIT collagen, cartilage, assoc. with type II and XI fibrils COL9A1, COL9A2, COL9A3 – EDM2 and EDM3
X hypertrophic and mineralizing cartilage COL10A1 Schmid metaphyseal dysplasia
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
XIV FACIT collagen COL14A1
XV COL15A1
XVI COL16A1
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
XIX FACIT collagen COL19A1
XX COL20A1
XXI FACIT collagen COL21A1
XXII COL22A1
XXIII MACIT collagen – COL23A1
XXIV COL24A1
XXV COL25A1
XXVI EMID2
XXVII COL27A1
XXVIII COL28A1
XXIX epidermal collagen COL29A1 Atopic dermatitis[31]

In addition to the above mentioned disorders, excessive deposition of collagen occurs in scleroderma.

Staining

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.

Synthesis

Action of lysyl oxidase

Amino acids

Collagen has an unusual amino acid composition and sequence:

  • Glycine (Gly) is found at almost every third residue
  • Proline (Pro) makes up about 17% of collagen
  • Collagen contains two uncommon derivative amino acids not directly inserted during translation. These amino acids are found at specific locations relative to glycine and are modified post-translationally by different enzymes, both of which require vitamin C as a cofactor.

Cortisol stimulates degradation of (skin) collagen into amino acids.[32]

Collagen I formation

Most collagen forms in a similar manner, but the following process is typical for type I:

  1. Inside the cell
    1. Two types of peptide chains are formed during translation on ribosomes along the rough endoplasmic reticulum (RER): alpha-1 and alpha-2 chains. These peptide chains (known as preprocollagen) have registration peptides on each end and a signal peptide.
    2. Polypeptide chains are released into the lumen of the RER.
    3. Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains.
    4. Hydroxylation of lysine and proline amino acids occurs inside the lumen. This process is dependent on ascorbic acid (Vitamin C) as a cofactor.
    5. Glycosylation of specific hydroxylysine residues occurs.
    6. Triple helical structure is formed inside the endoplasmic reticulum from each two alpha-1 chains and one alpha-2 chain.
    7. Procollagen is shipped to the Golgi apparatus, where it is packaged and secreted by exocytosis.
  2. Outside the cell
    1. Registration peptides are cleaved and tropocollagen is formed by procollagen peptidase.
    2. Multiple tropocollagen molecules form collagen fibrils, via covalent cross-linking (aldol reaction) by lysyl oxidase which links hydroxylysine and lysine residues. Multiple collagen fibrils form into collagen fibers.
    3. Collagen may be attached to cell membranes via several types of protein, including fibronectin and integrin.

Synthetic pathogenesis

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.

An autoimmune disease such as lupus erythematosus or rheumatoid arthritis[33] may attack healthy collagen fibers.

Many bacteria and viruses have virulence factors which destroy collagen or interfere with its production.

Characteristics

Collagen 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 skin.[34][35] Along with soft keratin, it is responsible for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging.[36][37] 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.

Uses

Collagen has a wide variety of applications, from food to medical. For instance, it is used in cosmetic surgery and burns surgery. Hydrolyzed collagen can play an important role in weight management, as a protein, it can be advantageously used for its satiating power.[citation needed] It is widely used in the form of collagen casings for sausages.

If collagen is sufficiently denatured, e.g. by heating, the three tropocollagen strands separate partially or completely into globular domains, containing a different secondary structure to the normal collagen polyproline II (PPII), e.g. random coils. This process describes the formation of gelatin, which is used in many foods, including flavored gelatin desserts. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries.[38] From a nutritional point of view, collagen and gelatin are a poor-quality sole source of protein since they do not contain all the essential amino acids in the proportions that the human body requires—they are not 'complete proteins' (as defined by food science, not that they are partially structured). Manufacturers of collagen-based dietary supplements claim that their products can improve skin and fingernail quality as well as joint health. However, mainstream scientific research has not shown strong evidence to support these claims.[citation needed] Individuals with problems in these areas are more likely to be suffering from some other underlying condition (such as normal aging, dry skin, arthritis etc.) rather than just a protein deficiency.

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.[39] 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.[40]

Medical uses

Cardiac applications

The four dense collagen valve rings, the central body of the heart and the cardiac skeleton of the heart are histologically bound to the myocardium. Collagen contribution to heart performance summarily represents an essential, unique and moving solid anchor opposed to the fluid mechanics of blood within the heart. This structure is an impermeable firewall that excludes both blood and electrical influence (except through anatomical channels) from the upper to the lower chambers of the heart. As proof, one could posit that atrial fibrillation almost never deteriorates to ventricular fibrillation. Individual valvular leaflets are held in sail shape by collagen under variable pressure. Calcium deposition within collagen occurs as a natural consequence of aging. Calcium rich fixed points in an otherwise moving display of blood and muscle enable current cardiac imaging technology to arrive at ratios essentially stating blood in cardiac input and blood out cardiac output. Specified imaging such as calcium scoring illustrates the utility of this methodology, especially in an aging patient subject to pathology of the collagen underpinning.

Cosmetic surgery

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. Both human and bovine collagen is widely used as dermal fillers for treatment of wrinkles and skin aging.[37] Some points of interest are:

  1. when used cosmetically, there is a chance of allergic reactions causing prolonged redness; however, this can be virtually eliminated by simple and inconspicuous patch testing prior to cosmetic use, and
  2. most medical collagen is derived from young beef cattle (bovine) from certified BSE (bovine spongiform encephalopathy) free animals. Most manufacturers use donor animals from either "closed herds", or from countries which have never had a reported case of BSE such as Australia, Brazil and New Zealand.
  3. porcine (pig) tissue is also widely used for producing collagen sheet for a variety of surgical purposes.
  4. alternatives using the patient's own fat, hyaluronic acid or polyacrylamide gels which are readily available.

Reconstructive surgical uses

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 as a pill commercially as a joint mobility supplement with poor references.[41] Because proteins are broken down into amino acids before absorption, there is no reason for orally ingested collagen to affect connective tissue in the body, except through the effect of individual amino acid supplementation.

Although it cannot be absorbed through the skin, collagen is now being used as a main ingredient for some cosmetic makeup.[42]

Collagen is also frequently used in scientific research applications for cell culture, studying cell behavior and cellular interactions with the extracellular environment.[43] Suppliers such as Trevigen manufacture rat and bovine Collagen I and mouse Collagen IV.

Wound care management uses

Collagen is one of the body’s key natural resources and a component of skin tissue that can benefit all stages of the wound healing process. When collagen is made available to the wound bed, closure can occur. Wound deterioration, followed sometimes by procedures such as amputation, can thus be avoided.

Throughout the 4 phases of wound healing, collagen performs the following functions in wound healing: • Guiding Function: Collagen fibers serve to guide fibroblasts. Fibroblasts migrate along a connective tissue matrix. • Chemotactic Properties: The large surface area available on collagen fibers can attract fibrogenic cells which help in healing. • Nucleation: Collagen, in the presence of certain neutral salt molecules can act as a nucleating agent causing formation of fibrillar structures. A collagen wound dressing might serve as a guide for orienting new collagen deposition and capillary growth. • Hemostatic properties: Blood platelets interact with the collagen to make a hemostatic plug.

Paleontology and Archaeology

Because the synthesis of collagen requires a high level of atmospheric oxygen, complex animals may not have been able to evolve until the atmosphere was oxygenic enough for collagen synthesis.[44] The origin of collagen may have allowed cuticle, shell and muscle formation. However, the preservation of collagen in the fossil record is very scarce.[45] There is mounting evidence—which remains controversial—that collagen has been preserved in dinosaur specimens dated as long ago as 80 million years ago.[46]

Also worth noting are the actinofibrils, collagen fibers present on the wings of pterosaurs.

Collagen is regularly extracted from the bones of prehistoric animals for use in radiocarbon dating and stable isotope analysis. The integrity of the molecule can be assessed with a number of measurements (collagen yield, C:N ratio, %C and %N) [23]. With respect to radiometric dating, extracted collagen produces a 'more pure' form of carbon that can be dated than does bulk bone, which contains a high amount of carbonated apatite, which is prone to exchange with environmental sources of carbon, causing contamination. Stable isotope analysis of carbon and nitrogen are commonly used to study diet in past populations of humans, as well as to reconstruct ecological conditions.

Art

Julian Voss-Andreae's sculpture Unraveling Collagen (2005), stainless steel, height 11 ft 3 in (3.40 m).

Using the atomic coordinates deposited in the Protein Data Bank, German-American artist Julian Voss-Andreae has created sculptures based on the structure of collagen and other proteins.[47] In Unraveling Collagen the triangular cut-outs reveal the dominant force lines, reminiscent of contemporary steel construction.[48][49]

See also

References

  1. ^ Müller, Werner E. G. (2003). "The Origin of Metazoan Complexity: Porifera as Integrated Animals". Integrated Computational Biology 43 (1): 3–10. doi:10.1093/icb/43.1.3. 
  2. ^ Di Lullo, Gloria A.; Sweeney, Shawn M.; Körkkö, Jarmo; Ala-Kokko, Leena & San Antonio, James D. (2002). "Mapping the Ligand-binding Sites and Disease-associated Mutations on the Most Abundant Protein in the Human, Type I Collagen". J. Biol. Chem. 277 (6): 4223–4231. doi:10.1074/jbc.M110709200. PMID 11704682. 
  3. ^ Sikorski, Zdzisław E. (2001). Chemical and Functional Properties of Food Proteins. Boca Raton: CRC Press. p. 242. ISBN 1566769604. 
  4. ^ Wyckoff, R.; Corey, R. & Biscoe, J. (1935). "X-ray reflections of long spacing from tendon". Science 82 (2121): 175–176. doi:10.1126/science.82.2121.175. PMID 17810172. 
  5. ^ Clark, G.; Parker, E.; Schaad, J. & Warren, W. J. (1935). "New measurements of previously unknown large interplanar spacings in natural materials". J. Amer. Chem. Soc 57 (8): 1509. doi:10.1021/ja01311a504. 
  6. ^ "GNR — A Tribute - Resonance - October 2001". http://www.ias.ac.in/resonance/Oct2001/Oct2001p2-5.html. 
  7. ^ Leonidas, Demetres D.; et al., GB; Jardine, AM; Li, S; Shapiro, R; Acharya, KR (2001). "Binding of Phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography". Protein Science 10 (8): 1669–1676. doi:10.1110/ps.13601. PMC 2374093. PMID 11468363. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2374093. 
  8. ^ Subramanian, Easwara (2001). "Obituary: G.N. Ramachandran". Nature Structural & Molecular Biology 8 (6): 489–491. doi:10.1038/88544. PMID 11373614. 
  9. ^ Fraser, R. D.; MacRae, T. P. & Suzuki, E. (1979). "Chain conformation in the collagen molecule". J Mol Biol 129 (3): 463–481. doi:10.1016/0022-2836(79)90507-2. PMID 458854. 
  10. ^ Okuyama, K.; et al., K; Arnott, S; Takayanagi, M; Kakudo, M (1981). "Crystal and molecular structure of a collagen-like polypeptide (Pro-Pro-Gly)10". J Mol Biol 152 (2): 427–443. doi:10.1016/0022-2836(81)90252-7. PMID 7328660. 
  11. ^ Traub, W.; Yonath, A. & Segal, D. M. (1969). "On the molecular structure of collagen". Nature 221 (5184): 914–917. doi:10.1038/221914a0. 
  12. ^ Bella, J.; Eaton, M.; Brodsky, B.; Berman, H. M. (1994). "Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution". Science 266 (5182): 75–81. doi:10.1126/science.7695699. PMID 7695699. 
  13. ^ a b Hulmes, D. J. & Miller, A. (1979). "Quasi-hexagonal molecular packing in collagen fibrils". Nature 282 (5741): 878–880. doi:10.1038/282878a0. PMID 514368. 
  14. ^ Jesior, J. C.; Miller, A. & Berthet-Colominas, C. (1980). "Crystalline three-dimensional packing is general characteristic of type I collagen fibrils". FEBS Lett 113 (2): 238–240. doi:10.1016/0014-5793(80)80600-4. PMID 7389896. 
  15. ^ Fraser, R. D. B. & MacRae, T. P. (1981). "Unit cell and molecular connectivity in tendon collagen". Int. J. Biol. Macromol. 3 (3): 193–200. doi:10.1016/0141-8130(81)90063-5. 
  16. ^ Fraser, R. D.; MacRae, T. P.; Miller, A. (1987). "Molecular packing in type I collagen fibrils". J Mol Biol 193 (1): 115–125. doi:10.1016/0022-2836(87)90631-0. PMID 3586015. 
  17. ^ Wess, T. J.; et al., AP; Wess, L; Miller, A (1998). "Molecular packing of type I collagen in tendon". J Mol Biol 275 (2): 255–267. doi:10.1006/jmbi.1997.1449. PMID 9466908. 
  18. ^ Raspanti, M.; Ottani, V.; Ruggeri, A. (1990). "Subfibrillar architecture and functional properties of collagen: a comparative study in rat tendons". J Anat. 172: 157–164. PMC 1257211. PMID 2272900. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1257211. 
  19. ^ Holmes, D. F.; Gilpin, C. J.; Baldock, C.; Ziese, U.; Koster, A. J.; Kadler, K. E. (2001). "Corneal collagen fibril structure in three dimensions: Structural insights into fibril assembly, mechanical properties, and tissue organization". PNAS 98 (13): 7307–7312. doi:10.1073/pnas.111150598. PMC 34664. PMID 11390960. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=34664. 
  20. ^ Holmes, D. F.; Kadler, KE (2006). "The 10+4 microfibril structure of thin cartilage fibrils". PNAS 103 (46): 17249–17254. doi:10.1073/pnas.0608417103. PMC 1859918. PMID 17088555. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1859918. 
  21. ^ a b c Orgel, J. P.; et al., TC; Miller, A; Wess, TJ (2006). "Microfibrillar structure of type I collagen in situ". PNAS 103 (24): 9001–9005. doi:10.1073/pnas.0502718103. PMC 1473175. PMID 16751282. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1473175. 
  22. ^ >narayanaswamy, Radhakrishnan; Shanmugasamy, Sangeetha (2011). "Bioinformatics in crosslinking chemistry of collagen with selective crosslinkers". BMC 4: 399. doi:10.1186/1756-0500-4-399. 
  23. ^ a b c d e f g Szpak, Paul (2011). "Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis". Journal of Archaeological Science 38 (12): 3358–3372. doi:10.1016/j.jas.2011.07.022. http://uwo.academia.edu/PaulSzpak/Papers/827788/Fish_Bone_Chemistry_and_Ultrastructure_Implications_for_Taphonomy_and_Stable_Isotope_Analysis. 
  24. ^ Hulmes, D. J. (2002). "Building collagen molecules, fibrils, and suprafibrillar structures". J Struct Biol 137 (1–2): 2–10. doi:10.1006/jsbi.2002.4450. PMID 12064927. 
  25. ^ a b Hulmes, D. J. (1992). "The collagen superfamily—diverse structures and assemblies". Essays Biochem 27: 49–67. PMID 1425603. 
  26. ^ Perumal, S.; Antipova, O. & Orgel, J. P. (2008). "Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis". PNAS 105 (8): 2824–2829. doi:10.1073/pnas.0710588105. PMC 2268544. PMID 18287018. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2268544. 
  27. ^ Sweeney, S. M.; et al., JP; Fertala, A; McAuliffe, JD; Turner, KR; Di Lullo, GA; Chen, S; Antipova, O et al. (2008). "Candidate Cell and Matrix Interaction Domains on the Collagen Fibril, the Predominant Protein of Vertebrates". J Biol Chem 283 (30): 21187–21197. doi:10.1074/jbc.M709319200. PMC 2475701. PMID 18487200. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2475701. 
  28. ^ Twardowski, T.; et al., A.; Orgel, J. P.R.O.; San Antonio, J. D. (2007). "Type I collagen and collagen mimetics as angiogenesis promoting superpolymers". Curr Pharm Des 13 (35): 3608–3621. doi:10.2174/138161207782794176. http://www.ingentaconnect.com/content/ben/cpd/2007/00000013/00000035/art00009. 
  29. ^ M. Minary-Jolandan and M.-F. Yu, "Nanomechanical Heterogeneity in the Gap and Overlap Regions of Type I Collagen Fibrils with Implications for Bone Heterogeneity", Biomacromolecules 10, 2565 (2009)
  30. ^ Sabiston textbook of surgery board review, 7th edition. Chapter 5 wound healing, question 14
  31. ^ Söderhäll, C.; Marenholz, I.; Kerscher, T.; Rüschendorf, F; Rüschendorf, F.; Esparza-Gordillo, J.; et al., C; Mayr, G et al. (2007). "Variants in a Novel Epidermal Collagen Gene (COL29A1) Are Associated with Atopic Dermatitis". PLoS Biology 5 (9): e242. doi:10.1371/journal.pbio.0050242. PMC 1971127. PMID 17850181. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1971127. 
  32. ^ Houck, J. C.; Sharma, V. K.; Patel, Y. M.; Gladner, J. A. (1968). "Induction of Collagenolytic and Proteolytic Activities by AntiInflammatory Drugs in the Skin and Fibroblasts". Biochemical Pharmacology 17 (10): 2081–2090. doi:10.1016/0006-2952(68)90182-2. PMID 4301453. 
  33. ^ Al-Hadithy, H.; et al., DA; Addison, IE; Goldstone, AH; Snaith, ML (1982). "Neutrophil function in systemic lupus erythematosus and other collagen diseases". Ann Rheum Dis 41 (1): 33–38. doi:10.1136/ard.41.1.33. PMC 1000860. PMID 7065727. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1000860. 
  34. ^ Fratzl, P. (2008). Collagen: Structure and Mechanics. New York: Springer. ISBN 038773905X. 
  35. ^ Buehler, M. J. (2006). "Nature designs tough collagen: Explaining the nanostructure of collagen fibrils". PNAS 103 (33): 12285–12290. doi:10.1073/pnas.0603216103. PMC 1567872. PMID 16895989. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1567872. 
  36. ^ Structure of Skin | The Aging Skin
  37. ^ a b Dermal Fillers | The Ageing Skin
  38. ^ "Gelatin's Advantages: Health, Nutrition and Safety". http://www.gmap-gelatin.com/gelatin_adv.html. 
  39. ^ Walker, Amélie A. (May 21, 1998). "Oldest Glue Discovered". Archaeology. http://www.archaeology.org/online/news/glue.html. 
  40. ^ Ennker, I. C.; et al., JüRgen; Schoon, Doris; Schoon, Heinz Adolf; Rimpler, Manfred; Hetzer, Roland (1994). "Formaldehyde-free collagen glue in experimental lung gluing". Ann Thorac Surg. 57 (6): 1622–1627. doi:10.1016/0003-4975(94)90136-8. PMID 8010812. http://ats.ctsnetjournals.org/cgi/content/abstract/57/6/1622. 
  41. ^ "Hydrolyzed Collagen pills usages". http://www.articlecat.com/Article/Hydrolyzed-Collagen--Protein-Hydrate/21273. 
  42. ^ "www.articlesbase.com". http://www.articlesbase.com/skin-care-articles/can-collagen-be-absorbed-into-the-skin-or-is-it-all-just-one-big-hoax-674325.html. [dead link]
  43. ^ Blow, Nathan (2009). "Cell culture: building a better matrix". Nature Methods 6 (8): 619–622. doi:10.1038/nmeth0809-619. 
  44. ^ http://facstaff.gpc.edu/~pgore/geology/geo102/cambrian.htm
  45. ^ We, K. M. T. O. (1996). "Fossil preservation in the Burgess Shale". Lethaia 29 (1): 107–108. doi:10.1111/j.1502-3931.1996.tb01844.x.  edit
  46. ^ Schweitzer, H. .; Zheng, W. .; Organ, L. .; Avci, R. .; Suo, Z. .; Freimark, M. .; Lebleu, S. .; Duncan, B. . et al.; Wenxia Zheng,1 Chris L. Organ,3 Recep Avci,4 Zhiyong Suo,4 Lisa M. Freimark,5 Valerie S. Lebleu,6,7 Michael B. Duncan,6,7 Matthew G. Vander Heiden,8 John M. Neveu,9 William S. Lane,9 John S. Cottrell,10 John R. Horner,11 Lewis C. Cantley,5,12 Raghu Kalluri,6,7,13 John M. Asara5,14,* (May 2009). "Biomolecular Characterization and Protein Sequences of the Campanian Hadrosaur B. Canadensis". Science 324 (5927): 626–631. Bibcode 2009Sci...324..626S. doi:10.1126/science.1165069. ISSN 0036-8075. PMID 19407199.  edit
  47. ^ "PDB Community Focus: Julian Voss-Andreae, Protein Sculptor". Protein Data Bank Newsletter (32). Winter 2007. ftp://ftp.wwpdb.org/pub/pdb/doc/newsletters/rcsb_pdb/news32_jan07.pdf. 
  48. ^ Ward, Barbara (April 2006). "'Unraveling Collagen' structure to be installed in Orange Memorial Park Sculpture Garden". Expert Rev. Proteomics 3 (2) (2): 174. doi:10.1586/14789450.3.2.169. http://www.future-drugs.com/doi/pdf/10.1586/14789450.3.2.169. 
  49. ^ Interview with J. Voss-Andreae "Seeing Below the Surface" in Seed Magazine

External links


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Collagen — is the principal protein of the skin, tendons, cartilage, bone and connective tissue. * * * The major protein (comprising over half of that in mammals) of the white fibers of connective tissue, cartilage, and bone, that is insoluble in water but… …   Medical dictionary

  • Collagen — Col la*gen, n. [Gr. ko lla glue + gen.] (Physiol. Chem.) The chemical basis of ordinary connective tissue, as of tendons or sinews and of bone. On being boiled in water it becomes gelatin or glue. [1913 Webster] …   The Collaborative International Dictionary of English

  • collagen — collagen. См. коллаген. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • Collagen — Collagen, Glutin (s.d.) gebendes Gewebe …   Pierer's Universal-Lexikon

  • collagen — structural protein of connective tissue, 1843, from Fr. collagène, from Gk. kolla glue + gen giving birth to (see GEN (Cf. gen)) …   Etymology dictionary

  • collagen — ► NOUN ▪ the main structural protein found in animal connective tissue, yielding gelatin when boiled. ORIGIN French collagène, from Greek kolla glue …   English terms dictionary

  • collagen — [käl′ə jən] n. [< Gr kolla, glue + GEN] a fibrous protein found in connective tissue, bone, and cartilage collagenic [käl′əjən′ik] adj. collagenous [kə laj′ə nəs] adj …   English World dictionary

  • collagen — collagenous /keuh laj euh neuhs/, adj. /kol euh jeuhn/, n. Biochem. any of a class of extracellular proteins abundant in higher animals, esp. in the skin, bone, cartilage, tendon, and teeth, forming strong insoluble fibers and serving as… …   Universalium

  • collagen — [[t]kɒ̱ləʤən[/t]] N UNCOUNT Collagen is a protein that is found in the bodies of people and animals. It is often used as an ingredient in cosmetics or is injected into the face in cosmetic surgery, in order to make the skin look younger. The… …   English dictionary

  • Collagen — Kollagen (internationalisierte Schreibweise Collagen; Betonung auf der letzten Silbe) ist ein nur bei Menschen und Tieren vorkommendes Strukturprotein des Bindegewebes (genauer: der extrazellulären Matrix). Im menschlichen Körper ist Kollagen mit …   Deutsch Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”