Collagen /ˈkɒlədʒɪn/ is the main structural protein in the
extracellular space in the various connective tissues in animal
bodies. As the main component of connective tissue, it is the most
abundant protein in mammals, making up from 25% to 35% of the
whole-body protein content.
Collagen consists of amino acids wound
together to form triple-helices to form of elongated fibrils. It is
mostly found in fibrous tissues such as tendons, ligaments and skin.
Depending upon the degree of mineralization, collagen tissues may be
rigid (bone), compliant (tendon), or have a gradient from rigid to
compliant (cartilage). It is also abundant in corneas, cartilage,
bones, blood vessels, the gut, intervertebral discs, and the dentin in
teeth. In muscle tissue, it serves as a major component of the
Collagen constitutes one to two percent of muscle tissue,
and accounts for 6% of the weight of strong, tendinous muscles. The
fibroblast is the most common cell that creates collagen. Gelatin,
which is used in food and industry, is collagen that has been
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". This
refers to the compound's early use in the process of boiling the skin
and tendons of horses and other animals to obtain glue.
1 Types of collagen
2 Medical uses
2.1 Cardiac applications
2.2 Cosmetic surgery
2.4 Tissue regeneration
2.5 Reconstructive surgical uses
3 As a supplement
4 Basic research
5 Veterinary use
Collagen I formation
7.3 Synthetic pathogenesis
8 Molecular structure
9 Associated disorders
14 See also
16 External links
Types of collagen
Collagen occurs in many places throughout the body. Over 90% of the
collagen in the human body, however, is type I.
So far, 28 types of collagen have been identified and described. They
can be divided into several groups according to the structure they
Fibrillar (Type I, II, III, V, XI)
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
MACIT (Membrane Associated Collagens with Interrupted Triple Helices)
(Type XIII, XVII)
Other (Type VI, VII)
The five most common types are:
Type I: skin, tendon, vasculature, organs, 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
Type V: cell surfaces, hair and placenta
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
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
should never deteriorate to ventricular fibrillation.
layered in variable densities with cardiac 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.
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. Some points of interest are:
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.
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.
As the skeleton forms the structure of the body, it is vital that it
maintains its strength, even after breaks and injuries.
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.
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
Reconstructive surgical uses
Collagens are widely employed in the construction of the artificial
skin substitutes used in the management of severe burns and
wounds. 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
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
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.
Throughout the 4 phases of wound healing, collagen performs the
following functions in wound healing:
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.
Blood platelets interact with the collagen to
make a hemostatic plug.
As a supplement
When hydrolyzed, collagen is reduced to small peptides which can be
ingested in the form of dietary supplement or functional foods and
beverages with intent to aid joint and bone health and enhance skin
Hydrolyzed collagen has a much
smaller molecular weight in comparison to native collagen or gelatin,
study suggests that more than 90% of hydrolyzed collagen is digested
and available as small peptides in the blood stream within one hour.
From the blood the peptides (containing hydroxyproline) are
transported into the target tissues, e.g. skin, bones and cartilage,
where the peptides act as building blocks for local cells and help
boost the production of new collagen fibers.
Collagen is used in laboratory studies for cell culture, studying cell
behavior and cellular interactions with the extracellular
Some studies have shown efficacy of collagen supplementation for dogs
with osteoarthritis pain, alone or in combination with other
nutraceuticals like glucosamine and chondroitin.
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). 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.
Abundance in mammal skin
Abundance in fish skin
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. Because the
hydroxylase enzymes that perform these reactions require vitamin C as
a cofactor, a long-term deficiency in this vitamin results in impaired
collagen synthesis and scurvy. These hydroxylation reactions are
catalyzed by two different enzymes: prolyl-4-hydroxylase and
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.  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.
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).
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.
Pre-pro-peptide to pro-collagen: Three modifications of the
pre-pro-peptide occur leading to the formation of the alpha peptide:
The signal peptide on the
N-terminal is dissolved, and the molecule is
now known as propeptide (not procollagen).
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).
Glycosylation occurs by adding either glucose or galactose monomers
onto the hydroxyl groups that were placed onto lysines, but not on
Once these modifications have taken place, three of the hydroxylated
and glycosylated propeptides twist into a triple helix forming
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.
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
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.
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 tropocollogen
is known as a collagen fibril.
Action of lysyl oxidase
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.
Hydroxyproline derived from proline
Hydroxylysine derived from lysine - depending on the type of collagen,
varying numbers of hydroxylysines are glycosylated (mostly having
Cortisol stimulates degradation of (skin) collagen into amino
Collagen I formation
Most collagen forms in a similar manner, but the following process is
typical for type I:
Inside the cell
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.
Polypeptide chains are released into the lumen of the RER.
Signal peptides are cleaved inside the RER and the chains are now
known as pro-alpha chains.
Hydroxylation of lysine and proline amino acids occurs inside the
lumen. This process is dependent on ascorbic acid (vitamin C) as a
Glycosylation of specific hydroxylysine residues occurs.
Triple alpha helical structure is formed inside the endoplasmic
reticulum from two alpha-1 chains and one alpha-2 chain.
Procollagen is shipped to the Golgi apparatus, where it is packaged
and secreted by exocytosis.
Outside the cell
Registration peptides are cleaved and tropocollagen is formed by
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 may be attached to cell membranes via several types of
protein, including fibronectin, laminin, fibulin and integrin.
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 may attack healthy collagen fibers.
Many bacteria and viruses secrete virulence factors, such as the
enzyme collagenase, which destroys collagen or interferes with its
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
Three polypeptides coil to form tropocollagen. Many tropocollagens
then bind together to form a fibril, and many of these then form a
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.
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. 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. 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. 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. 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". 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
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). Larger
fibrillar bundles are formed with the aid of several different classes
of proteins (including different collagen types), glycoproteins and
proteoglycans to form the different types of mature tissues from
alternate combinations of the same key players. Collagen's
insolubility was a barrier to the study of monomeric collagen until it
was found that tropocollagen from young animals can be extracted
because it is not yet fully crosslinked. However, advances in
microscopy techniques (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.
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. 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.
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)
Type I collagen gives bone its tensile strength.
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
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
Osteogenesis imperfecta, Ehlers–Danlos syndrome, Infantile cortical
hyperostosis a.k.a. Caffey's disease
Hyaline cartilage, makes up 50% of all cartilage protein. Vitreous
humour of the eye.
Collagenopathy, types II and XI
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
Ehlers–Danlos syndrome, Dupuytren's contracture
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
Most interstitial tissue, assoc. with type I, associated with placenta
COL5A1, COL5A2, COL5A3
Ehlers–Danlos syndrome (Classical)
Most interstitial tissue, assoc. with type I
COL6A1, COL6A2, COL6A3, COL6A5
Ulrich myopathy, Bethlem myopathy, Atopic dermatitis
Forms anchoring fibrils in dermoepidermal junctions
Epidermolysis bullosa dystrophica
Some endothelial cells
Posterior polymorphous corneal dystrophy 2
FACIT collagen, cartilage, assoc. with type II and XI fibrils
COL9A1, COL9A2, COL9A3
EDM2 and EDM3
Hypertrophic and mineralizing cartilage
Schmid metaphyseal dysplasia
Collagenopathy, types II and XI
FACIT collagen, interacts with type I containing fibrils, decorin and
Transmembrane collagen, interacts with integrin a1b1, fibronectin and
components of basement membranes like nidogen and perlecan.
FACIT collagen, also known as undulin
Transmembrane collagen, also known as BP180, a 180 kDa protein
Bullous pemphigoid and certain forms of junctional epidermolysis
Source of endostatin
In addition to the above-mentioned disorders, excessive deposition of
collagen occurs in scleroderma.
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
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.
Chondrodysplasias – Skeletal disorder believed to be caused by a
mutation in type 2 collagen, further research is being conducted to
Ehlers-Danlos syndrome – Six different types of this disorder, which
lead to deformities in connective tissue, are known. 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.
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
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.
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 is at an
increased risk of developing it themselves as there is a hereditary
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. Along with elastin and soft keratin, it is responsible
for skin strength and elasticity, and its degradation leads to
wrinkles that accompany aging. It strengthens blood vessels and
plays a role in tissue development. It is present in the cornea and
lens of the eye in crystalline form. It may be one of the most
abundant proteins in the fossil record, given that it appears to
fossilize frequently, even in bones from the
Collagen has a wide variety of applications, from food to medical. For
instance, it is used in cosmetic surgery and burn 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.
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.
was used by Egyptians about 4,000 years ago, and Native Americans used
it in bows about 1,500 years ago. The oldest glue in the world,
carbon-dated as more than 8,000 years old, was found to be
collagen—used as a protective lining on rope baskets and embroidered
fabrics, and to hold utensils together; also in crisscross decorations
on human skulls.
Collagen normally converts to gelatin, but
survived due to 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
Gelatin-resorcinol-formaldehyde glue (and with formaldehyde replaced
by less-toxic pentanedial and ethanedial) has been used to repair
experimental incisions in rabbit lungs.
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. 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 of
Ramachandran, which provided an essentially correct model of the
molecule's quaternary structure although this model still
required some refinement. [clarification needed] 
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. As with its
monomeric structure, several conflicting models alleged that either
the packing arrangement of collagen molecules is 'sheet-like' or
microfibrillar. The microfibrillar structure of collagen
fibrils in tendon, cornea and cartilage has been directly imaged by
electron microscopy. The microfibrillar structure of tail
tendon, as described by Fraser, Miller, and Wess (amongst others), was
modeled 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. 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.
The evolution of collagens was a fundamental step in the early
evolution of life, supporting the coalescence of multicellular life
Collagen D-banding is viable as periodic formation of ridging on all
fibrils forming collagen. D-bands are created due to the
semi-crystalline formation of the collagen within the fibrils. The
pattern exhibited by D-banding is consistently independent of fibril
diameter. When undergoing deformation, collagen fibrils may lose
their D-banding, making the disappearance of the d-bands an indicator
of the type of damage undergone by then tendon fibrils.
Hydrolyzed collagen, a common form in which collagen is sold as a
Osteoid, collagen-containing component of bone
Collagenase, the enzyme involved in collagen breakdown and remodeling
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