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Collagen

From Wikipedia, the free encyclopedia

Tropocollagen molecule: three left-handed procollagens (red, green, blue) join to form a right-handed triple helical tropocollagen.

Collagen (/ˈkɒlədʒən/) is the main structural protein in the extracellular matrix of a body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals.[1] 25% to 35% of a mammalian body's protein content is collagen. Amino acids are bound together to form a triple helix of elongated fibril[2] known as a collagen helix. The collagen helix is mostly found in connective tissue such as cartilage, bones, tendons, ligaments, and skin. Vitamin C is vital for collagen synthesis, while Vitamin E improves its production.

HCR-FISH visualization of collagen expression in the Iberian ribbed newt

Depending upon the degree of mineralization, collagen tissues may be rigid (bone) or compliant (tendon) or have a gradient from rigid to compliant (cartilage). Collagen is also abundant in corneas, blood vessels, the gut, intervertebral discs, and the dentin in teeth.[3] In muscle tissue, it serves as a major component of the endomysium. Collagen constitutes 1% to 2% of muscle tissue and accounts for 6% of the weight to skeletal muscle.[4] The fibroblast is the most common cell creating collagen in a body. Gelatin, which is used in food and industry, is collagen that was irreversibly hydrolyzed using heat, basic solutions, or weak acids.[5]

Etymology

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Collagen

The name collagen comes from the Greek κόλλα (kólla), meaning "glue", and suffix -γέν, -gen, denoting "producing".[6][7]

Collagen types

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Over 90% of the collagen in the human body is type I & III collagen.[8] However, as of 2011, 28 types of human collagen have been identified, described, and divided into several groups according to the structure they form.[9] All of the types contain at least one triple helix.[9] The number of types shows collagen's diverse functionality.[10]

  • Fibrillar (Type I, II, III, V, XI)
  • Non-fibrillar
    • FACIT (Fibril Associated Collagens with Interrupted Triple Helices) (Type IX, XII, XIV, XIX, XXI)
    • 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)
    • Microfibril forming (Type VI)
    • Anchoring fibrils (Type VII)

The five most common types are:[11]

In human biology

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Cardiac

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The collagenous cardiac skeleton which includes the four heart valve rings, is histologically, elastically and uniquely bound to cardiac muscle. The cardiac skeleton also includes the separating septa of the heart chambers – the interventricular septum and the atrioventricular septum. Collagen contribution to the measure of cardiac performance summarily represents a continuous torsional force opposed to the fluid mechanics of blood pressure emitted from the heart. The collagenous structure that divides the upper chambers of the heart from the lower chambers is an impermeable membrane that excludes both blood and electrical impulses through typical physiological means. With support from collagen, atrial fibrillation never deteriorates to ventricular fibrillation. Collagen is layered in variable densities with smooth muscle mass. The mass, distribution, age, and density of collagen all contribute to the compliance required to move blood back and forth. Individual cardiac valvular leaflets are folded into shape by specialized collagen under variable pressure. Gradual calcium deposition within collagen occurs as a natural function of aging. Calcified points within collagen matrices show contrast in a moving display of blood and muscle, enabling 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 understood within the category of connective tissue disease.[citation needed]

Bone grafts

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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.[12]

Tissue regeneration

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Collagen scaffolds are used in tissue regeneration, whether in sponges,[13] thin sheets,[14] gels,[15] or fibers.[16] Collagen has favorable properties for tissue regeneration, such as pore structure, permeability, hydrophilicity, and stability in vivo. Collagen scaffolds also support deposition of cells, such as osteoblasts and fibroblasts, and once inserted, facilitate growth to proceed normally.[17]

Reconstructive surgical uses

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Collagens are widely employed in the construction of artificial skin substitutes used in the management of severe burns and wounds.[18][19] 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.[20]

Wound healing

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Collagen is one of the body's key natural resources and a component of skin tissue that can benefit all stages of wound healing.[21] 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 and is thus 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.[18]

Throughout the four phases of wound healing, collagen performs the following functions:

  • 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.
  • Hemostatic properties: Blood platelets interact with the collagen to make a hemostatic plug.

Basic research

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Collagen is used in laboratory studies for cell culture, studying cell behavior and cellular interactions with the extracellular environment.[22] Collagen is also widely used as a bioink for 3D bioprinting and biofabrication of 3D tissue models.

Biology

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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).[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.[24]

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

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First, a three-dimensional stranded structure is assembled with amino acids glycine and proline as its principal components. This is not yet collagen but is 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 a triple helix structure to collagen. Because the hydroxylase enzymes performing these reactions require vitamin C as a cofactor, a long-term deficiency in this vitamin results in impaired collagen synthesis and scurvy.[25] These hydroxylation reactions are catalyzed by two different enzymes: prolyl 4-hydroxylase[26] and lysyl hydroxylase. The reaction consumes one ascorbate molecule per hydroxylation.[27] The synthesis of collagen occurs inside and outside of a 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 another common form of collagen. All types of collagens are triple helices, and the differences lie in the make-up of their alpha peptides created in step 2.

  1. Transcription of mRNA: About 44 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 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 preprocollagen.
  3. Pre-pro-peptide to pro-collagen: Three modifications of the pre-pro-peptide occur leading to the formation of the alpha peptide:
    1. The signal peptide on the N-terminal is removed, 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 hydroxyl groups that were placed onto lysines, but not on prolines.
    4. Once these modifications have taken place, three of the hydroxylated and glycosylated propeptides twist into a triple helix forming procollagen. Procollagen still has unwound ends, which will be later trimmed. 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 fibrillar collagen.
  6. Formation of the collagen fibril: lysyl oxidase, an extracellular copper-dependent 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 tropocollagen is known as a collagen fibril.
Action of lysyl oxidase

Amino acids

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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 unusual 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.[28]

Collagen I formation

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

  1. Inside the cell
    1. Two types of alpha chains – alpha-1 and alpha 2, are formed during translation on ribosomes along the rough endoplasmic reticulum (RER). These peptide chains known as preprocollagen, have registration peptides on each end and a signal peptide.[29]
    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 and consumes ascorbic acid (vitamin C) as a cofactor.
    5. Glycosylation of specific hydroxylysine residues occurs.
    6. Triple alpha helical structure is formed inside the endoplasmic reticulum from two alpha-1 chains and one alpha-2 chain.
    7. Procollagen is shipped to the Golgi apparatus, where it is packaged and secreted into extracellular space 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, laminin, fibulin and integrin.

Molecular structure

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A single collagen molecule, 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.[24] 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.[24] 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.[24] The lower proline and hydroxyproline contents of cold-water fish and other poikilotherm animals leads to their collagen having a lower thermal stability than mammalian collagen.[24] This lower thermal stability means that gelatin derived from fish collagen is not suitable for many food and industrial applications.

The tropocollagen subunits spontaneously self-assemble, with regularly staggered ends, into even larger arrays in the extracellular spaces of tissues.[30][31] Additional assembly of fibrils is guided by fibroblasts, which deposit fully formed fibrils from fibripositors. In the fibrillar collagens, molecules are staggered to adjacent molecules by about 67 nm (a unit that is referred to as 'D' and changes depending upon the hydration state of the aggregate). 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".[32] These overlap and gap regions are retained as microfibrils assemble into fibrils, and are thus viewable using electron microscopy. The triple helical tropocollagens in the microfibrils are arranged in a quasihexagonal packing pattern.[32][33]

The D-period of collagen fibrils results in visible 67nm bands when observed by electron microscopy.

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).[34] 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.[31] 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 (i.e. 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.[35] 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.[36][37] 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.[38]

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 hydroxylapatite (approximately) Ca10(OH)2(PO4)6.[39] Type I collagen gives bone its tensile strength.

Associated disorders

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Collagen-related diseases most commonly arise from genetic defects or nutritional deficiencies that affect the biosynthesis, assembly, posttranslational 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[40]
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 FACIT collagen 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 FACIT collagen 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

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One thousand mutations have been identified in 12 out of more than 20 types of collagen. These mutations can lead to various diseases at the tissue level.[41]

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.[42]

Chondrodysplasias – Skeletal disorder believed to be caused by a mutation in type 2 collagen, further research is being conducted to confirm this.[43]

Ehlers–Danlos syndrome – Thirteen different types of this disorder, which lead to deformities in connective tissue, are known.[44] Some of the rarer types can be lethal, leading to the rupture of arteries. Each syndrome is caused by a different mutation. For example, the vascular type (vEDS) of this disorder is caused by a mutation in collagen type 3.[45]

Alport syndrome – Can be passed on genetically, usually as X-linked dominant, but also as both an autosomal dominant and autosomal recessive disorder, those with the condition have problems with their kidneys and eyes, loss of hearing can also develop during the childhood or adolescent years.[46]

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 with the disorder is at an increased risk of developing it themselves since there is a hereditary link.[41]

Animal harvesting

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When not synthesized, collagen can be harvested from animal skin. This has led to deforestation as has occurred in Paraguay where large collagen producers buy large amounts of cattle hides from regions that have been clear-cut for cattle grazing.[47]

Characteristics

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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.[48][49] Along with elastin and soft keratin, it is responsible for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging.[50] 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.[51]

Mechanical properties

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Collagen is a complex hierarchical material with mechanical properties that vary significantly across different scales.

On the molecular scale, atomistic and course-grained modeling simulations, as well as numerous experimental methods, have led to several estimates of the Young's modulus of collagen at the molecular level. Only above a certain strain rate is there a strong relationship between elastic modulus and strain rate, possibly due to the large number of atoms in a collagen molecule.[52] The length of the molecule is also important, where longer molecules have lower tensile strengths than shorter ones due to short molecules having a large proportion of hydrogen bonds being broken and reformed.[53]

On the fibrillar scale, collagen has a lower modulus compared to the molecular scale, and varies depending on geometry, scale of observation, deformation state, and hydration level.[52] By increasing the crosslink density from zero to 3 per molecule, the maximum stress the fibril can support increases from 0.5 GPa to 6 GPa.[54]

Limited tests have been done on the tensile strength of the collagen fiber, but generally it has been shown to have a lower Young's modulus compared to fibrils.[55]

When studying the mechanical properties of collagen, tendon is often chosen as the ideal material because it is close to a pure and aligned collagen structure. However, at the macro, tissue scale, the vast number of structures that collagen fibers and fibrils can be arranged into results in highly variable properties. For example, tendon has primarily parallel fibers, whereas skin consists of a net of wavy fibers, resulting in a much higher strength and lower ductility in tendon compared to skin. The mechanical properties of collagen at multiple hierarchical levels is given.

Young's Modulus of Collagen at Multiple Hierarchical Levels
Hierarchical Level Young's Modulus
Molecular (via atomistic modeling) 2.4-7 GPa[56][57]
Fibril 0.2-0.8 GPa[58]
Fiber (measured from cross-linked rat tail tendon) 1.10 GPa[59]
Fiber (measured from non-cross-linked rat tail tendon) 50-250 MPa[59]

Collagen is known to be a viscoelastic solid. When the collagen fiber is modeled as two Kelvin-Voigt models in series, each consisting of a spring and a dashpot in parallel, the strain in the fiber can be modeled according to the following equation:

where α, β, and γ are defined materials properties, εD is fibrillar strain, and εT is total strain.[60]

Uses

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A salami and the collagen casing (below) it came in

Collagen has a wide variety of applications, from food to medical.[61] In the medical industry, it is used in cosmetic surgery and burn surgery. In the food sector, one use example is in casings for sausages.

If collagen is subject to sufficient denaturation, such as 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) of 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. It is also used as a dietary supplement, and has been advertised as a potential remedy against the ageing process.[62][63][64]

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, to hold utensils together, and in crisscross decorations on human skulls.[65] Collagen normally converts to gelatin, but survived due to dry conditions. Animal glues are thermoplastic, softening again upon reheating, 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.[66]

Cosmetics

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Bovine collagen is widely used in dermal fillers for aesthetic correction of wrinkles and skin aging.[67] Collagen cremes are also widely sold even though collagen cannot penetrate the skin because its fibers are too large.[68] Collagen is a vital protein in skin, hair, nails, and other tissues. Its production decreases with age and factors like sun damage and smoking. Collagen supplements, derived from sources like fish and cattle, are marketed to improve skin, hair, and nails. Studies show some skin benefits, but these supplements often contain other beneficial ingredients, making it unclear if collagen alone is effective. There's minimal evidence supporting collagen's benefits for hair and nails. Overall, the effectiveness of oral collagen supplements is not well-proven, and focusing on a healthy lifestyle and proven skincare methods like sun protection is recommended.[69]

History

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The molecular and packing structures of collagen 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.[70][71] Research then concentrated on the conformation of the collagen monomer, producing several competing models, although correctly dealing with the conformation of each individual peptide chain. The triple-helical "Madras" model, proposed by G. N. Ramachandran in 1955, provided an accurate model of quaternary structure in collagen.[72][73][74][75][76] This model was supported by further studies of higher resolution in the late 20th century.[77][78][79][80]

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.[33][81][82] As with its monomeric structure, several conflicting models propose either that the packing arrangement of collagen molecules is 'sheet-like', or is microfibrillar.[83][84] The microfibrillar structure of collagen fibrils in tendon, cornea and cartilage was imaged directly by electron microscopy in the late 20th century and early 21st century.[85][86][87] The microfibrillar structure of rat tail tendon was modeled as being closest to the observed structure, although it oversimplified the topological progression of neighboring collagen molecules, and so did not predict the correct conformation of the discontinuous D-periodic pentameric arrangement termed microfibril.[32][88][89]

See also

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References

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  1. ^ Di Lullo GA, Sweeney SM, Korkko J, Ala-Kokko L, San Antonio JD (February 2002). "Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen". The Journal of Biological Chemistry. 277 (6): 4223–4231. doi:10.1074/jbc.M110709200. PMID 11704682.
  2. ^ "Leather grown using biotechnology is about to hit the catwalk". The Economist. 26 August 2017. Archived from the original on 1 September 2017. Retrieved 2 September 2017.
  3. ^ Britannica Concise Encyclopedia 2007
  4. ^ Sikorski ZE (2001). Chemical and Functional Properties of Food Proteins. Boca Raton, Florida: CRC Press. p. 242. ISBN 978-1-56676-960-0.
  5. ^ Bogue RH (1923). "Conditions Affecting the Hydrolysis of Collagen to Gelatin". Industrial and Engineering Chemistry. 15 (11): 1154–59. doi:10.1021/ie50167a018.
  6. ^ O.E.D. 2nd Edition 2005
  7. ^ Müller WE (February 2003). "The origin of metazoan complexity: porifera as integrated animals". Integrative and Comparative Biology. 43 (1): 3–10. CiteSeerX 10.1.1.333.3174. doi:10.1093/icb/43.1.3. PMID 21680404. S2CID 17232196.
  8. ^ Sabiston textbook of surgery board review, 7th edition. Chapter 5 wound healing, question 14
  9. ^ a b Ricard-Blum S (January 2011). "The collagen family". Cold Spring Harbor Perspectives in Biology. 3 (1): a004978. doi:10.1101/cshperspect.a004978. PMC 3003457. PMID 21421911.
  10. ^ Franzke CW, Bruckner P, Bruckner-Tuderman L (February 2005). "Collagenous transmembrane proteins: recent insights into biology and pathology". The Journal of Biological Chemistry. 280 (6): 4005–4008. doi:10.1074/jbc.R400034200. PMID 15561712.
  11. ^ Ashokkumar M, Ajayan PM (3 April 2021). "Materials science perspective of multifunctional materials derived from collagen". International Materials Reviews. 66 (3): 160–87. Bibcode:2021IMRv...66..160A. doi:10.1080/09506608.2020.1750807. ISSN 0950-6608. S2CID 216270520.
  12. ^ Cunniffe G, O'Brien F (2011). "Collagen scaffolds for orthopedic regenerative medicine". The Journal of the Minerals, Metals & Materials Society. 63 (4): 66–73. Bibcode:2011JOM....63d..66C. doi:10.1007/s11837-011-0061-y. S2CID 136755815.
  13. ^ Geiger M, Li RH, Friess W (November 2003). "Collagen sponges for bone regeneration with rhBMP-2". Advanced Drug Delivery Reviews. 55 (12): 1613–1629. doi:10.1016/j.addr.2003.08.010. PMID 14623404.
  14. ^ Bunyaratavej P, Wang HL (February 2001). "Collagen membranes: a review". Journal of Periodontology. 72 (2): 215–229. doi:10.1902/jop.2001.72.2.215. hdl:2027.42/141506. PMID 11288796.
  15. ^ Drury JL, Mooney DJ (November 2003). "Hydrogels for tissue engineering: scaffold design variables and applications". Biomaterials. 24 (24): 4337–4351. doi:10.1016/S0142-9612(03)00340-5. PMID 12922147.
  16. ^ Tonndorf R, Aibibu D, Cherif C (January 2020). "Collagen multifilament spinning". Materials Science & Engineering. C, Materials for Biological Applications. 106: 110105. doi:10.1016/j.msec.2019.110105. PMID 31753356. S2CID 202227968.
  17. ^ Oliveira SM, Ringshia RA, Legeros RZ, Clark E, Yost MJ, Terracio L, et al. (August 2010). "An improved collagen scaffold for skeletal regeneration". Journal of Biomedical Materials Research. Part A. 94 (2): 371–379. doi:10.1002/jbm.a.32694. PMC 2891373. PMID 20186736.
  18. ^ a b Singh O, Gupta SS, Soni M, Moses S, Shukla S, Mathur RK (January 2011). "Collagen dressing versus conventional dressings in burn and chronic wounds: a retrospective study". Journal of Cutaneous and Aesthetic Surgery. 4 (1): 12–16. doi:10.4103/0974-2077.79180. PMC 3081477. PMID 21572675.
  19. ^ Gould LJ (January 2016). "Topical Collagen-Based Biomaterials for Chronic Wounds: Rationale and Clinical Application". Advances in Wound Care. 5 (1): 19–31. doi:10.1089/wound.2014.0595. PMC 4717516. PMID 26858912.
  20. ^ "Collagen and Rosehip Extract Sachet". Alaina Pharma. Archived from the original on 4 July 2016. Retrieved 31 May 2021.
  21. ^ Birbrair A, Zhang T, Files DC, Mannava S, Smith T, Wang ZM, et al. (November 2014). "Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner". Stem Cell Research & Therapy. 5 (6): 122. doi:10.1186/scrt512. PMC 4445991. PMID 25376879.
  22. ^ Blow N (2009). "Cell culture: building a better matrix". Nature Methods. 6 (8): 619–22. doi:10.1038/nmeth0809-619. S2CID 33438539.
  23. ^ Brodsky B, Persikov AV (1 January 2005). "Molecular structure of the collagen triple helix". Advances in Protein Chemistry. 70: 301–339. doi:10.1016/S0065-3233(05)70009-7. ISBN 978-0120342709. PMID 15837519. S2CID 20879450.
  24. ^ a b c d e Szpak P (2011). "Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis". Journal of Archaeological Science. 38 (12): 3358–72. Bibcode:2011JArSc..38.3358S. doi:10.1016/j.jas.2011.07.022.
  25. ^ Peterkofsky B (December 1991). "Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy". The American Journal of Clinical Nutrition. 54 (6 Suppl): 1135S–1140S. doi:10.1093/ajcn/54.6.1135s. PMID 1720597.
  26. ^ Gorres KL, Raines RT (April 2010). "Prolyl 4-hydroxylase". Critical Reviews in Biochemistry and Molecular Biology. 45 (2): 106–124. doi:10.3109/10409231003627991. PMC 2841224. PMID 20199358.
  27. ^ Myllylä R, Majamaa K, Günzler V, Hanauske-Abel HM, Kivirikko KI (May 1984). "Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase". The Journal of Biological Chemistry. 259 (9): 5403–5405. doi:10.1016/S0021-9258(18)91023-9. PMID 6325436.
  28. ^ Houck JC, Sharma VK, Patel YM, Gladner JA (October 1968). "Induction of collagenolytic and proteolytic activities by anti-inflammatory drugs in the skin and fibroblast". Biochemical Pharmacology. 17 (10): 2081–2090. doi:10.1016/0006-2952(68)90182-2. PMID 4301453.
  29. ^ "preprocollagen". The Free Dictionary.
  30. ^ Hulmes DJ (2002). "Building collagen molecules, fibrils, and suprafibrillar structures". Journal of Structural Biology. 137 (1–2): 2–10. doi:10.1006/jsbi.2002.4450. PMID 12064927.
  31. ^ a b Hulmes DJ (1992). "The collagen superfamily--diverse structures and assemblies". Essays in Biochemistry. 27: 49–67. PMID 1425603.
  32. ^ a b c Orgel JP, Irving TC, Miller A, Wess TJ (June 2006). "Microfibrillar structure of type I collagen in situ". Proceedings of the National Academy of Sciences of the United States of America. 103 (24): 9001–9005. Bibcode:2006PNAS..103.9001O. doi:10.1073/pnas.0502718103. PMC 1473175. PMID 16751282.
  33. ^ a b Hulmes DJ, Miller A (1979). "Quasi-hexagonal molecular packing in collagen fibrils". Nature. 282 (5741): 878–880. Bibcode:1979Natur.282..878H. doi:10.1038/282878a0. PMID 514368. S2CID 4332269.
  34. ^ Perumal S, Antipova O, Orgel JP (February 2008). "Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis". Proceedings of the National Academy of Sciences of the United States of America. 105 (8): 2824–2829. Bibcode:2008PNAS..105.2824P. doi:10.1073/pnas.0710588105. PMC 2268544. PMID 18287018.
  35. ^ Buchanan JK, Zhang Y, Holmes G, Covington AD, Prabakar S (2019). "Role of X-ray Scattering Techniques in Understanding the Collagen Structure of Leather" (PDF). ChemistrySelect. 4 (48): 14091–102. doi:10.1002/slct.201902908. ISSN 2365-6549. S2CID 212830367. Archived (PDF) from the original on 27 January 2022.
  36. ^ Sweeney SM, Orgel JP, Fertala A, McAuliffe JD, Turner KR, Di Lullo GA, et al. (July 2008). "Candidate cell and matrix interaction domains on the collagen fibril, the predominant protein of vertebrates". The Journal of Biological Chemistry. 283 (30): 21187–21197. doi:10.1074/jbc.M709319200. PMC 2475701. PMID 18487200.
  37. ^ Twardowski T, Fertala A, Orgel JP, San Antonio JD (2007). "Type I collagen and collagen mimetics as angiogenesis promoting superpolymers". Current Pharmaceutical Design. 13 (35): 3608–3621. doi:10.2174/138161207782794176. PMID 18220798.
  38. ^ Minary-Jolandan M, Yu MF (September 2009). "Nanomechanical heterogeneity in the gap and overlap regions of type I collagen fibrils with implications for bone heterogeneity". Biomacromolecules. 10 (9): 2565–2570. doi:10.1021/bm900519v. PMID 19694448.
  39. ^ Ross, M. H. and Pawlina, W. (2011) Histology, 6th ed., Lippincott Williams & Wilkins, p. 218.
  40. ^ Söderhäll C, Marenholz I, Kerscher T, Rüschendorf F, Esparza-Gordillo J, Worm M, et al. (September 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.
  41. ^ a b Mahajan VB, Olney AH, Garrett P, Chary A, Dragan E, Lerner G, et al. (November 2010). "Collagen XVIII mutation in Knobloch syndrome with acute lymphoblastic leukemia". American Journal of Medical Genetics. Part A. 152A (11): 2875–2879. doi:10.1002/ajmg.a.33621. PMC 2965270. PMID 20799329.
  42. ^ Gajko-Galicka A (2002). "Mutations in type I collagen genes resulting in osteogenesis imperfecta in humans" (PDF). Acta Biochimica Polonica. 49 (2): 433–441. doi:10.18388/abp.2002_3802. PMID 12362985. Archived (PDF) from the original on 7 June 2013.
  43. ^ Horton WA, Campbell D, Machado MA, Chou J (December 1989). "Type II collagen screening in the human chondrodysplasias". American Journal of Medical Genetics. 34 (4): 579–583. doi:10.1002/ajmg.1320340425. PMID 2624272.
  44. ^ Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. (March 2017). "The 2017 international classification of the Ehlers-Danlos syndromes". American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 175 (1): 8–26. doi:10.1002/ajmg.c.31552. PMID 28306229. S2CID 4440499.
  45. ^ Hamel BC, Pals G, Engels CH, van den Akker E, Boers GH, van Dongen PW, et al. (June 1998). "Ehlers-Danlos syndrome and type III collagen abnormalities: a variable clinical spectrum". Clinical Genetics. 53 (6): 440–446. doi:10.1111/j.1399-0004.1998.tb02592.x. PMID 9712532. S2CID 39089732.
  46. ^ Kashtan CE (1993). "Alport Syndrome and Thin Basement Membrane Nephropathy". In Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP (eds.). GeneReviews. Vol. Collagen IV-Related Nephropathies. Seattle WA: University of Washington, Seattle. PMID 20301386.
  47. ^ Alexander I (9 October 2024). "Collagen and meat giants fuel deforestation and rights violations in Paraguay: Report". Mongabay Environmental News. Retrieved 9 October 2024.
  48. ^ Fratzl P (2008). Collagen: Structure and Mechanics. New York: Springer. ISBN 978-0-387-73905-2.
  49. ^ Buehler MJ (August 2006). "Nature designs tough collagen: explaining the nanostructure of collagen fibrils". Proceedings of the National Academy of Sciences of the United States of America. 103 (33): 12285–12290. Bibcode:2006PNAS..10312285B. doi:10.1073/pnas.0603216103. PMC 1567872. PMID 16895989.
  50. ^ Dermal Fillers | The Ageing Skin Archived 13 May 2011 at the Wayback Machine. Pharmaxchange.info. Retrieved on 21 April 2013.
  51. ^ Zylberberg L, Laurin M (2011). "Analysis of fossil bone organic matrix by transmission electron microscopy". Comptes Rendus Palevol. 11 (5–6): 357–66. doi:10.1016/j.crpv.2011.04.004.
  52. ^ a b Gautieri A, Vesentini S, Redaelli A, Buehler MJ (February 2011). "Hierarchical structure and nanomechanics of collagen microfibrils from the atomistic scale up". Nano Letters. 11 (2): 757–766. Bibcode:2011NanoL..11..757G. doi:10.1021/nl103943u. hdl:1721.1/77587. PMID 21207932.
  53. ^ Pradhan SM, Katti DR, Katti KS (2011). "Steered Molecular Dynamics Study of Mechanical Response of Full Length and Short Collagen Molecules". Journal of Nanomechanics and Micromechanics. 1 (3): 104–110. doi:10.1061/(ASCE)NM.2153-5477.0000035. ISSN 2153-5434.
  54. ^ Buehler MJ (January 2008). "Nanomechanics of collagen fibrils under varying cross-link densities: atomistic and continuum studies". Journal of the Mechanical Behavior of Biomedical Materials. 1 (1): 59–67. doi:10.1016/j.jmbbm.2007.04.001. PMID 19627772.
  55. ^ Gentleman E, Lay AN, Dickerson DA, Nauman EA, Livesay GA, Dee KC (September 2003). "Mechanical characterization of collagen fibers and scaffolds for tissue engineering". Biomaterials. 24 (21): 3805–3813. doi:10.1016/s0142-9612(03)00206-0. PMID 12818553.
  56. ^ Vesentini S, Fitié CF, Montevecchi FM, Redaelli A (June 2005). "Molecular assessment of the elastic properties of collagen-like homotrimer sequences". Biomechanics and Modeling in Mechanobiology. 3 (4): 224–234. doi:10.1007/s10237-004-0064-5. PMID 15824897.
  57. ^ Buehler MJ (August 2006). "Atomistic and continuum modeling of mechanical properties of collagen: Elasticity, fracture, and self-assembly". Journal of Materials Research. 21 (8): 1947–1961. Bibcode:2006JMatR..21.1947B. doi:10.1557/jmr.2006.0236. ISSN 2044-5326.
  58. ^ van der Rijt JA, van der Werf KO, Bennink ML, Dijkstra PJ, Feijen J (September 2006). "Micromechanical testing of individual collagen fibrils". Macromolecular Bioscience. 6 (9): 697–702. doi:10.1002/mabi.200600063. PMID 16967482.
  59. ^ a b Gentleman E, Lay AN, Dickerson DA, Nauman EA, Livesay GA, Dee KC (September 2003). "Mechanical characterization of collagen fibers and scaffolds for tissue engineering". Biomaterials. 24 (21): 3805–3813. doi:10.1016/S0142-9612(03)00206-0. PMID 12818553.
  60. ^ Puxkandl R, Zizak I, Paris O, Keckes J, Tesch W, Bernstorff S, et al. (February 2002). Bailey AJ, Macmillan J, Shrewry PR, Tatham AS (eds.). "Viscoelastic properties of collagen: synchrotron radiation investigations and structural model". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 357 (1418): 191–197. doi:10.1098/rstb.2001.1033. PMC 1692933. PMID 11911776.
  61. ^ "4 Head-To-Toe Ways That Collagen Can Improve Your Health". Penn Medicine. Philadelphia, PA: University of Pennsylvania Health System. 4 November 2018. Archived from the original on 19 September 2020. Retrieved 3 April 2023.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  62. ^ Al-Atif H (February 2022). "Collagen Supplements for Aging and Wrinkles: A Paradigm Shift in the Fields of Dermatology and Cosmetics". Dermatology Practical & Conceptual. 12 (1): e2022018. doi:10.5826/dpc.1201a18. PMC 8824545. PMID 35223163.
  63. ^ Lawton G (1 April 2023). "The radical new theory that wrinkles actually cause ageing". New Scientist.
  64. ^ Campos LD, Santos Junior Vd, Pimentel JD, Carregã GL, Cazarin CB (2023). "Collagen supplementation in skin and orthopedic diseases: A review of the literature". Heliyon. 9 (4): e14961. Bibcode:2023Heliy...914961C. doi:10.1016/j.heliyon.2023.e14961. ISSN 2405-8440. PMC 10102402. PMID 37064452.
  65. ^ Walker AA (21 May 1998). "Oldest Glue Discovered". Archaeology. Archived from the original on 17 December 2005.
  66. ^ Ennker IC, Ennker J, Schoon D, Schoon HA, Rimpler M, Hetzer R (June 1994). "Formaldehyde-free collagen glue in experimental lung gluing". The Annals of Thoracic Surgery. 57 (6): 1622–1627. doi:10.1016/0003-4975(94)90136-8. PMID 8010812.
  67. ^ Wasley A, Mendonça E, Zuker F (6 March 2023). "Global craze for collagen linked to Brazilian deforestation". The Guardian. ISSN 0261-3077. Retrieved 6 March 2023.
  68. ^ "Collagen". Harvard T.H. Chan School of Public Health: The Nutrition Source. 26 May 2021. Retrieved 6 March 2023.
  69. ^ "Considering collagen drinks and supplements?". Harvard Health Blog. Harvard Health Publishing. 12 April 2023. Retrieved 19 July 2024.
  70. ^ Wyckoff RW, Corey RB, Biscoe J (August 1935). "X-Ray Reflections of Long Spacing from Tendon". Science. 82 (2121): 175–176. Bibcode:1935Sci....82..175W. doi:10.1126/science.82.2121.175. PMID 17810172.
  71. ^ Clark G, Parker E, Schaad J, Warren WJ (1935). "New measurements of previously unknown large interplanar spacings in natural materials". J. Am. Chem. Soc. 57 (8): 1509. doi:10.1021/ja01311a504.
  72. ^ Ramachandran GN, Kartha G (September 1955). "Structure of collagen". Nature. 176 (4482): 593–595. Bibcode:1955Natur.176..593R. doi:10.1038/176593a0. PMID 13265783. S2CID 33745131.
  73. ^ Ramachandran GN, Kartha G (August 1954). "Structure of collagen". Nature. 174 (4423): 269–270. Bibcode:1954Natur.174..269R. doi:10.1038/174269c0. PMID 13185286. S2CID 4284147.
  74. ^ Balasubramanian, D . (October 2001). "GNR – A Tribute". Resonance. 6 (10): 2–4. doi:10.1007/BF02836961. S2CID 122261106. Archived from the original on 10 January 2014.
  75. ^ Leonidas DD, Chavali GB, Jardine AM, Li S, Shapiro R, Acharya KR (August 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.
  76. ^ Subramanian E (June 2001). "G.N. Ramachandran". Nature Structural Biology. 8 (6): 489–491. doi:10.1038/88544. PMID 11373614. S2CID 7231304.
  77. ^ Fraser RD, MacRae TP, Suzuki E (April 1979). "Chain conformation in the collagen molecule". Journal of Molecular Biology. 129 (3): 463–481. doi:10.1016/0022-2836(79)90507-2. PMID 458854.
  78. ^ Okuyama K, Okuyama K, Arnott S, Takayanagi M, Kakudo M (October 1981). "Crystal and molecular structure of a collagen-like polypeptide (Pro-Pro-Gly)10". Journal of Molecular Biology. 152 (2): 427–443. doi:10.1016/0022-2836(81)90252-7. PMID 7328660.
  79. ^ Traub W, Yonath A, Segal DM (March 1969). "On the molecular structure of collagen". Nature. 221 (5184): 914–917. Bibcode:1969Natur.221..914T. doi:10.1038/221914a0. PMID 5765503. S2CID 4145093.
  80. ^ Bella J, Eaton M, Brodsky B, Berman HM (October 1994). "Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution". Science. 266 (5182): 75–81. Bibcode:1994Sci...266...75B. doi:10.1126/science.7695699. PMID 7695699.
  81. ^ Jésior JC, Miller A, Berthet-Colominas C (May 1980). "Crystalline three-dimensional packing is a general characteristic of type I collagen fibrils". FEBS Letters. 113 (2): 238–240. Bibcode:1980FEBSL.113..238J. doi:10.1016/0014-5793(80)80600-4. PMID 7389896. S2CID 40958154.
  82. ^ Fraser RD, MacRae TP (1981). "Unit cell and molecular connectivity in tendon collagen". International Journal of Biological Macromolecules. 3 (3): 193–200. doi:10.1016/0141-8130(81)90063-5.
  83. ^ Fraser RD, MacRae TP, Miller A (January 1987). "Molecular packing in type I collagen fibrils". Journal of Molecular Biology. 193 (1): 115–125. doi:10.1016/0022-2836(87)90631-0. PMID 3586015.
  84. ^ Wess TJ, Hammersley AP, Wess L, Miller A (January 1998). "Molecular packing of type I collagen in tendon". Journal of Molecular Biology. 275 (2): 255–267. doi:10.1006/jmbi.1997.1449. PMID 9466908.
  85. ^ Raspanti M, Ottani V, Ruggeri A (October 1990). "Subfibrillar architecture and functional properties of collagen: a comparative study in rat tendons". Journal of Anatomy. 172: 157–164. PMC 1257211. PMID 2272900.
  86. ^ Holmes DF, Gilpin CJ, Baldock C, Ziese U, Koster AJ, Kadler KE (June 2001). "Corneal collagen fibril structure in three dimensions: Structural insights into fibril assembly, mechanical properties, and tissue organization". Proceedings of the National Academy of Sciences of the United States of America. 98 (13): 7307–7312. Bibcode:2001PNAS...98.7307H. doi:10.1073/pnas.111150598. PMC 34664. PMID 11390960.
  87. ^ Holmes DF, Kadler KE (November 2006). "The 10+4 microfibril structure of thin cartilage fibrils". Proceedings of the National Academy of Sciences of the United States of America. 103 (46): 17249–17254. Bibcode:2006PNAS..10317249H. doi:10.1073/pnas.0608417103. PMC 1859918. PMID 17088555.
  88. ^ Okuyama K, Bächinger HP, Mizuno K, Boudko S, Engel J, Berisio R, et al. (September 2009). "Re: Microfibrillar structure of type I collagen in situ". Acta Crystallographica. Section D, Biological Crystallography. 65 (Pt 9): 1009–10. Bibcode:2009AcCrD..65.1007O. doi:10.1107/S0907444909023051. PMID 19690380.
  89. ^ Orgel J (2009). "On the packing structure of collagen: response 0to Okuyama et al.'s comment on Microfibrillar structure of type I collagen in situ". Acta Crystallographica Section D. D65 (9): 1009. Bibcode:2009AcCrD..65.1009O. doi:10.1107/S0907444909028741.
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