World Library  
Flag as Inappropriate
Email this Article

Collagen

Article Id: WHEBN0000006058
Reproduction Date:

Title: Collagen  
Author: World Heritage Encyclopedia
Language: English
Subject: Vitamin C, Integrin, Metastatic breast cancer, Cell encapsulation, List of cutaneous conditions
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Collagen

Collagen triple helix

Collagen is the main structural protein in the extracellular space in the various connective tissues in animals. As the main component of connective tissue, it is the most abundant protein in mammals,[1] making up from 25% to 35% of the whole-body protein content.

Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendons, ligaments and skin. It is also abundant in corneas, cartilage, bones, blood vessels, the gut, intervertebral discs and the dentin in teeth.[2] 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] The fibroblast is the most common cell that creates collagen.

Gelatin, which is used in food and industry, is collagen that has been irreversibly hydrolyzed. Collagen also has many medical uses in treating complications of the bones and skin.

The name collagen comes from the Greek κόλλα (kólla), meaning "glue", and suffix -γέν, -gen, denoting "producing".[4][5] This refers to the compound's early use in the process of boiling the skin and sinews of horses and other animals to obtain glue.

Types of collagen

Collagen occurs in many places throughout the body. Over 90% of the collagen in the human body, however, is type I.[6]

So far, 28 types of collagen have been identified and described. They can be divided into several groups according to the structure they form:

  • Fibrillar (Type I, II, III, V, XI)
  • Non-fibrillar
    • FACIT (Fibril Associated Collagens with Interrupted Triple Helices) (Type IX, XII, XIV, XVI, XIX)
    • Short chain (Type VIII, X)
    • Basement membrane (Type IV)
    • Multiplexin (Multiple Triple Helix domains with Interruptions) (Type XV, XVIII)
    • MACIT (Membrane Associated Collagens with Interrupted Triple Helices) (Type XIII, XVII)
    • Other (Type VI, VII)

The five most common types are:

  • Type I: bone (main component of the organic part of bone)
  • Type II: cartilage (main collagenous component of cartilage)
  • Type III: reticulate (main component of reticular fibers), commonly found alongside type I.
  • Type IV: forms basal lamina, the epithelium-secreted layer of the basement membrane.
  • Type V: cell surfaces, hair and placenta

Medical uses

Cardiac applications

The collagenous pressure. Gradual calcium deposition within collagen occurs as a natural consequence of aging. Calcium rich fixed points within collagen in a moving display of blood and muscle enables methods of cardiac imaging technology to arrive at ratios essentially stating blood in (cardiac input) and blood out (cardiac output). Pathology of the collagen underpinning of the heart is closely related to the category connective tissue disease.

Hydrolyzed type II collagen and osteoarthritis

A published study[7] reports that ingestion of a novel low molecular weight hydrolyzed chicken sternal cartilage extract, containing a matrix of hydrolyzed type II collagen, chondroitin sulfate, and hyaluronic acid, relieves joint discomfort associated with osteoarthritis. A randomized controlled trial (RCT) enrolling 80 subjects demonstrated that it was well tolerated with no serious adverse event and led to a significant improvement in joint mobility compared to the placebo group on days 35 (p = 0.007) and 70 (p < 0.001).

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.[8] 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.
  2. most medical collagen is derived from young beef cattle (bovine) from certified BSE-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.

Bone grafts

As the skeleton forms the structure of the body, it is vital that it maintains its strength, even after breaks and injuries. Collagen is used in bone grafting as it has a triple helical structure, making it a very strong molecule. It is ideal for use in bones, as it does not compromise the structural integrity of the skeleton. The triple helical structure of collagen prevents it from being broken down by enzymes, it enables adhesiveness of cells and it is important for the proper assembly of the extracellular matrix.[9]

Tissue regeneration

Collagen scaffolds are used in tissue regeneration, whether in sponges, thin sheets, or gels. Collagen has the correct properties for tissue regeneration such as pore structure, permeability, hydrophilicity and it is stable in vivo. Collagen scaffolds are also ideal for the deposition of cells, such as osteoblasts and fibroblasts and once inserted, growth is able to continue as normal in the tissue.[10]

Reconstructive surgical uses

Collagens are widely employed in the construction of the artificial skin substitutes used in the management of severe burns. These collagens may be derived from bovine, equine, porcine, or even human sources; and are sometimes used in combination with silicones, glycosaminoglycans, fibroblasts, growth factors and other substances.

Collagen is also sold commercially in pill form as a supplement to aid joint mobility. However, 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.

Collagen is also frequently used in scientific research applications for cell culture, studying cell behavior and cellular interactions with the extracellular environment.[11]

Wound care

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.

Collagen is a natural product, therefore it is used as a natural wound dressing and has properties that artificial wound dressings do not have. It is resistant against bacteria, which is of vital importance in a wound dressing. It helps to keep the wound sterile, because of its natural ability to fight infection. When collagen is used as a burn dressing, healthy granulation tissue is able to form very quickly over the burn, helping it to heal rapidly.[12]

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.

Chemistry

The collagen protein is 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).[13] 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.[13]

Amino acid Abundance in mammal skin
(residues/1000)
Abundance in fish skin
(residues/1000)
Glycine 329 339
Proline 126 108
Alanine 109 114
Hydroxyproline 95 67
Glutamic acid 74 76
Arginine 49 52
Aspartic acid 47 47
Serine 36 46
Lysine 29 26
Leucine 24 23
Valine 22 21
Threonine 19 26
Phenylalanine 13 14
Isoleucine 11 11
Hydroxylysine 6 8
Methionine 6 13
Histidine 5 7
Tyrosine 3 3
Cysteine 1 1
Tryptophan 0 0

Synthesis

First, a three-dimensional stranded structure is assembled, with the amino acids glycine and proline as its principal components. This is not yet collagen but its precursor, procollagen. Procollagen is then modified by the addition of hydroxyl groups to the amino acids proline and lysine. This step is important for later glycosylation and the formation of the triple helix structure of collagen. The hydroxylase enzymes that perform these reactions require Vitamin C as a cofactor, and a deficiency in this vitamin results in impaired collagen synthesis and the resulting disease scurvy[14] These hydroxylation reactions are catalyzed by two different enzymes: prolyl-4-hydroxylase[15] and lysyl-hydroxylase. Vitamin C also serves with them in inducing these reactions. in this service, one molecule of vitamin C is destroyed for each H replaced by OH. [16] 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. All types of collagens are triple helices, and the differences lie in the make-up of the alpha peptides created in step 2.

  1. Transcription of mRNA: About 34 genes are 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. It is now known as pre-pro-collagen.
  3. Alpha peptide to procollagen: Three modifications of the pre-pro-peptide occur 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 cross-linking of the alpha peptides. This enzymatic step 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 three 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, oligosaccharides (not monosaccharides as in step 3) are added, and then the procollagen 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. Defects in this step produce one of the many collagenopathies known as Ehlers-Danlos syndrome. This step is absent when synthesizing type III, a type of fibrilar collagen.
  6. Formation of the collagen fibril: 'Lysyl oxidase', an 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.
Action of lysyl oxidase

Amino acids

Collagen has an unusual amino acid composition and sequence:

  • Glycine is found at almost every third residue.
  • Proline 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.[17]

Collagen I formation

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

  1. Inside the cell
  2. Two types of alpha 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.
  3. Polypeptide chains are released into the lumen of the RER.
  4. Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains.
  5. Hydroxylation of lysine and proline amino acids occurs inside the lumen. This process is dependent on ascorbic acid (vitamin C) as a cofactor.
  6. Glycosylation of specific hydroxylysine residues occurs.
  7. Triple alpha helical structure is formed inside the endoplasmic reticulum from two alpha-1 chains and one alpha-2 chain.
  8. Procollagen is shipped to the Golgi apparatus, where it is packaged and secreted by exocytosis.
  9. Outside the cell
  10. Registration peptides are cleaved and tropocollagen is formed by procollagen peptidase.
  11. 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.
  12. Collagen may be attached to cell membranes via several types of protein, including fibronectin and integrin.
  13. 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 18th 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[18] may attack healthy collagen fibers.

    Many bacteria and viruses secrete virulence factors, such as the enzyme collagenase, which destroys collagen or interferes with its production.

    Molecular structure

    A single collagen molecule (also known as tropocollagen) is used to make up larger collagen aggregates, such as fibrils. It is approximately 300 nm long and 1.5 nm in diameter, and it is made up of three polypeptide strands (called alpha peptides, see step 2), each of which has the conformation of a left-handed helix – this should not be confused with the right-handed alpha helix. These three left-handed helices are twisted together into a right-handed triple helix or "super helix", a cooperative quaternary structure stabilized by many 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.

    Three polypeptides coil to form tropocollagen. Many tropocollagens then bind together to form a fibril, and many of these then form a fibre.

    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.[13] 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.[13] This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk fibroin.

    Collagen is not only 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 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.[13] 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.[13] This lower thermal stability means that gelatin derived from fish collagen is not suitable for many food and industrial applications.

    The tropocollagen [21]

    There is some [26]

    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 (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) Ca10(OH)2(PO4)6.[27] Type I collagen gives bone its tensile strength.

    Associated disorders

    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.

    Genetic Defects of Collagen Genes
    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, cornea, the endomysium surrounding muscle fibers, fibrocartilage, and the organic part of bones and teeth. COL1A1, COL1A2 Osteogenesis imperfecta, Ehlers–Danlos syndrome, Infantile cortical hyperostosis a.k.a. 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, COL6A5 Ulrich myopathy, Bethlem myopathy, Atopic dermatitis[28]
    VII Forms anchoring fibrils in dermoepidermal 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, also known as undulin 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

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

    Diseases

    One thousand mutations have been identified in twelve out of more than twenty types of collagen. These mutations can lead to various diseases at the tissue level.[29]

    Osteogenesis imperfecta – Caused by a mutation in type 1 collagen, dominant autosomal disorder, results in weak bones and irregular connective tissue, some cases can be mild while others can be lethal, mild cases have lowered levels of collagen type 1 while severe cases have structural defects in collagen.[30]

    Chondrodysplasias – Skeletal disorder believed to be caused by a mutation in type 2 collagen, further research is being conducted to confirm this.[31]

    Ehlers-Danlos Syndrome – Six different types of this disorder, which lead to deformities in connective tissue. Some types can be lethal, leading to the rupture of arteries. Each syndrome is caused by a different mutation, for example type four of this disorder is caused by a mutation in collagen type 3.[32]

    Alport syndrome – Can be passed on genetically, usually as X-linked dominant, but also as both an autosomal dominant and autosomal recessive disorder, sufferers have problems with their kidneys and eyes, loss of hearing can also develop in during the childhood or adolescent years.[33]

    Osteoporosis – Not inherited genetically, brought on with age, associated with reduced levels of collagen in the skin and bones, growth hormone injections are being researched as a possible treatment to counteract any loss of collagen.[34]

    Knobloch syndrome – Caused by a mutation in the COL18A1 gene that codes for the production of collagen XVIII. Patients present with protrusion of the brain tissue and degeneration of the retina, an individual who has family members suffering from the disorder are at an increased risk of developing it themselves as there is a hereditary link.[29]

    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.[35][36] Along with soft keratin, it is responsible for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging.[8] 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 may be one of the most abundant proteins in the fossil record, given that it appears to fossilize frequently, even in bones from the Mesozoic and Paleozoic.[37]

    Uses

    Collagen has a wide variety of applications, from food to medical. For instance, it is used in cosmetic surgery and burns surgery. It is widely used in the form of collagen casings for sausages, which are also used in the manufacture of musical strings.

    If collagen is subject to sufficient denaturation, 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 usually containing hydrolyzed collagen 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.[39] 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.[40] Collagen normally converts to gelatin, but survived due to 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.[41]

    History

    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.[42][43] Since that time, many prominent scholars, including Nobel laureates [21][59] Various cross linking agents like L-Dopaquinone, embeline, potassium embelate and 5-O-methyl embelin could be developed as potential cross-linking/stabilization agents of collagen preparation and its application as wound dressing sheet in clinical applications is enhanced.[60]

    See also

    References

    1. ^
    2. ^ Britannica Concise Encyclopedia 2007
    3. ^
    4. ^ O.E.D. 2nd Edition 2005
    5. ^
    6. ^ Sabiston textbook of surgery board review, 7th edition. Chapter 5 wound healing, question 14
    7. ^
    8. ^ a b Dermal Fillers | The Ageing Skin. Pharmaxchange.info. Retrieved on 2013-04-21.
    9. ^
    10. ^
    11. ^
    12. ^
    13. ^ a b c d e f
    14. ^
    15. ^
    16. ^
    17. ^
    18. ^
    19. ^
    20. ^ a b
    21. ^ a b c
    22. ^ a b
    23. ^
    24. ^
    25. ^
    26. ^
    27. ^ Ross, M. H. and Pawlina, W. (2011) Histology, 6th ed., Lippincott Williams & Wilkins, p. 218.
    28. ^
    29. ^ a b
    30. ^
    31. ^
    32. ^
    33. ^ Kashtan, CE (1993) "Collagen IV-Related Nephropathies (Alport Syndrome and Thin Basement Membrane Nephropathy)", in RA Pagon, TD Bird, CR Dolan, K Stephens & MP Adam (eds), GeneReviews, University of Washington, Seattle, Seattle WA PMID 20301386.
    34. ^
    35. ^
    36. ^
    37. ^
    38. ^
    39. ^ European Food Safety Authority - EFSA Panel on Dietetic Products, Nutrition and Allergies. Scientific Opinion on the substantiation of a health claim related to collagen hydrolysate and maintenance of joints pursuant to Article 13(5) of Regulation (EC) No 1924/20061. EFSA Journal 2011;9(7):2291.
    40. ^
    41. ^
    42. ^
    43. ^
    44. ^
    45. ^
    46. ^
    47. ^ a b c
    48. ^
    49. ^
    50. ^
    51. ^
    52. ^
    53. ^
    54. ^
    55. ^
    56. ^
    57. ^
    58. ^
    59. ^
    60. ^

    External links

    • 12 types of collagen
    • Database of type I and type III collagen mutations
    • Science.dirbix Collagen
    • Collagen Stability Calculator
    • Computer-generated animations of the assembly of Type I and Type IV Collagens
    • Integrin-Collagen interface, PMAP (The Proteolysis Map)—animation
    • Integrin-Collagen binding model, PMAP (The Proteolysis Map)—animation
    • Collagen-Integrin atomic detail, PMAP (The Proteolysis Map)—animation
    • Saad M. (1994) "Low resolution structure and packing investigations of collagen crystalline domains in tendon using Synchrotron Radiation X-rays, Structure factors determination, evaluation of Isomorphous Replacement methods and other modeling." PhD Thesis, Université Joseph Fourier Grenoble 1
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.