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Connective tissue
Eva Samcová
Types of tissues
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Connective tissue
Muscle tissue
Nervous tissue
Epithelial tissue
Connective tissue
• Most mammalian cells are located in tissues where they are
surrounded by a complex extracellular matrix (ECM), which is
the main part of connective tissue.
• The ECM contains three major classes of biomolecules : the
structural proteins (collagen, and elastin – fibrous
components), certain specialized proteins (fibrilin,
fibronectin, and laminin), and proteoglycans (amorphous
components). Moreover includes tissue fluid (water).
• The connective tissue thus includes three components :
• Cells (fibrocytes, osteocytes, myofibroblasts,
chondrocytes,etc.)
• Fibres (collagen, elastin, reticular)
• Basic amorphous substance (GAG, hyaluronic acid, structural
glycoproteins – fibronectin, laminin, etc,)
Functions of connective tissue
• Structural : creates housing enveloping cells and
organs, creates tendons, ligaments etc.
• Bone, adipose tissues and cartilages are specialized
types of connective tissue. Fluid connective tissues,
blood and lymphs are included in connective tissue,
too.
• Immune function : migrating cells (macrophages –
phagocytosis, plasma cells – production of
immunoglobulins, etc.)
• Nutritional function : environment for the exchange
of nutrition substances and waste products of
metabolism between cells and blood circulation.
Animal connective tissue are very variable
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Tendon and corina are flexible and firm
Bone is solid and dense
Cartilage absorb bumps and are flexible
Vitreous humour is soft and transparent
In all these cases, most of the tissue is formed
by extracellular matrix (ECM) and cells are
dispersed in it
ECM
• Amount of extracellular matrix is very
significant first of all in the connective tissue.
• Extracellular matrix is responsible for filter
properties of kidney, minimizes friction in the
joints, and enables the movement of cells .
• Variability is given by the type of the collagen,
its amount and by presence of the other
molecules.
Extracellular matrix
• It provides mechanical contact between cells and binds tissue
and cells together and by that ECM designes the shapes of
tissues.
• Importance of ECM is increased by the grasp of its role in
normal and pathological processes.
• Some of the embryonic cells must pass through ECM
• During inflammation, it gets to the biochemical changes in
ECM.
• ECM has the task in formation of metastasis, in migration of
tumorous cells through it to the blood capillary and then to
the lymphatic system
• Molecules of ECM are employed in rheumatoid arthritis and
osteoarthritis
• ECM is changing during aging process.
Main constituents of ECM
• Structural proteins : characteristic properties of
collagens are tensile, strength and flexibility
• Adhesive proteins : fibronectin, laminin and elastin
• Proteoglycans: act like packaging material, have
polar nature and many negative charges. They
compose from glycosaminoglycans bound to the
protein. Numerous protein molecules are associated
with an axis of hyaluronate
Where are formed ?
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In fibroblasts (skin, tendons,...)
In osteoblasts (bones)
In chondroblasts (cartilages)
The biosynthesis holds intracellulary and
products are released by exocytosis and
outside are arranged to huge cohesive
aggregates
• In case of collagens, enzyme collagenase splits
off propeptides by hydrolysis outside the cell
leading to the formation of fibrils
Extracellular matrix
Structure of collagen
Structure of collagen
Components of collagen
Collagens
• They account for 25% of all proteins in mammals
• It is fibrous protein that provides the structural framework for
tissues and organs. We can find it in discontinuous
connective tissue, bones, tendons, cartilages, skin, vessels
and cornea
• Collagens contain 33% of glycine and 21% proline and
hydroxyproline
• There are at least 12 variants of collagens in mammals
All collagens have structure of right-handed triple helix
• Every α chain has left-handed structure
• Every turn of triple helix contains 3 AA residues
• 1 molecule is formed by about 1000 AA residues
Biosynthesis
• The precursor molecule of collagen (preprocollagen) is
synthesized by ribosomes associated with the rER (like other
produced proteins). In the rER, signal sequences are released.
• The hydroxylation of proline and lysine and glycosylation of
hydroxylysine proceed in the rER (procollagen).
• The procollagen contains extensive peptides at either end.
Oxidation of cysteine groups within the propeptides
generates intramolecular and intermolecular disulfide bonds,
which ensure the correct assembly of the peptide strands to
form a triple helix.
• After formation of the triple helix, it does not occur the
hydroxylation of proline and lysine and glycosylation of
hydroxylysine. These proceses must be completed before
secretion into EMC (secreted by means of Golgi apparatus)
Biosynthesis, follow-up
• After secretion to the ECM, the extensive peptides
are removed.
• After their breakaway, the collagen fibrils are
formed.
• Collagen fibrils are stabilized by intra and
intermolecular crosslinks (lysyl oxidase)
• Lysyl oxidase contains copper – oxidative
deamination of ɛ-amino groups of some lysine and
hydroxylysine residues to yield aldehyde groups.
• Aldol condensation and formation of the Schiff´s
bases.
• Then the final structure which is characterized by
high tensile strength and a high degree of resistance
to proteinases.
Biosynhesis of collagen
Types of collagens
• There are at least 12 variants of collagen (19)
• Type I [α1(I)]2 α2(I) - (skin, tendons, bones,
dentine)
• Type II [α1(II)]3 - ( cartilage, vitreous humour)
• Type III [α1(III)]3 (fetal skin, uterus, blood vessels)
• Type IV (glomerulus, capsule of lens, basal
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membranes)
Type IV does not form cross striped fibrils, there are
places without repeating sequences
Arrangement of collagen in connective tissue
fibroblast
překližkové uspořádání
(řez kůží pulce)
Fibronectins
• Adhesive protein (glycoprotein) – filamentous dimer
• The fibronectin molecules are divided into different
domains.
• These domains bind to cell-surface receptors,
collagens, fibrin and various proteoglycans.
Fibronectin
• Fibronectin is secreted by the same cells as a
collagen.
• The bond to the cell is realized by receptors for
fibronectin - integrins
• Integrins are heterodimers, different types of α and
β polypeptide chains
• It interacts indirectly with microfilaments of actin
which are present in the cytosol (the way of
communication with intracellular space)
• The fibronectin participates on the migration of cells
by providing bind position.
Adhesive proteins
• Adhesive proteins connect the different constituents
of the extracellular matrix.
• These multifunctional proteins are characterized by
their ability to bind to several other matrix
constituents at the same time. The adhesive proteins
mediate the attachment of cells to the intracellular
matrix
Elastin
Elastin is a fibrous protein
Elastin gives tissues and organs the capacity to
stretch without tearing
It is abundant in ligaments, lungs, walls of arteries
and skin
Elastin does not contain repeating sequences of GlyX-YCross-linked structure gives the protein a rubber-like
elasticity.
Extracellulary is converted to heterocyclic structure
of desmosine.
Laminin
• After collagen, laminin is the protein occuring often in the
basal membrane – basal laminas with the ability to bind to
the other parts of ECM.
• Basal membrane is specialized type of ECM surrounding
epithelial and other cells (glomerulus – endothelial cells)
• Membrane of glomerulus is formed by 3 layers, the middle
lamina is surrounded by layer of epithelial cells and from the
opposite site by the layer of endothelial cells.
• Main components of basal membrane are 3 proteins :
laminin, entaktin and collagen IV.
• Laminin is composed from 3 different peptide chains,
connected into the structure of cross. It is actually
intermediator for connection of collagen and cell.
Laminin – follow-up
• Entactin, glycoprotein, also known as“nidogen“ binds to
laminin and is a major cell attachment factor.
• The membrane of glomerulus has an important role in
glomerular filtration, regulating the passage of large
molecules (most plasma proteins) across the glomerulus into
the renal tubule.
• On the other hand, only a small amount of the protein
albumin (69 kDa) passes through the normal glomerulus. The
pores in the glomerular membrane are large enough to allow
molecules up 8 nm to pass through.Albumin is smaller than
this pore size, but it is prevented from passing through easily
by the negative charges of heparan sulfate and of certain
sialic acid-containing glycoproteins present in the plasma.
• During damage of glomerulus (e.g. glomerulonephritis),pores
alter size and disposition of negatively charged of
macromolecules and relatively massive amounts of albumin
can pass through into the urine (albuminuria).
Basal lamina
Proteoglycans
• Against to glycoproteins, proteoglycans can contain as much
as 95% or more carbohydrate.
• Proteoglycans are high molecular weight polyanionic
substances consisting of many different GAG chains linked
covalently to a protein core.
• The long unbranched heteropolysacharide chains are made
up largely of disaccharide repeating units, in which one sugar
is a hexosamine and the other a uronic acid.
• Other common constituents of GAG are sulfate groups, linked
by ester bonds to certain monosaccharides or by amide bonds
to the amino group of glucosamine.
• Proteoglycans form solutions with high viscosity and elasticity
by absorbing large volumes of water.
Proteoglycans – follow-up
• This allows them to act in stabilizing and supporting
fibrous and cellular elements of tissues, as well as
contributing to the maintenance of water and salt
balance in the body.
• Increasingly more dynamic roles as receptors for
growth factors, transport proteins, and viruses are
being elucidated for the proteoglycans.
Proteoglycans
• huge complex molecules (Mr > 2.106)
• 5 % protein + 95 % polysaccharides
protein
chains
Hyaluronic acid
(hyaluronate)
Side chains
glycosaminoglycans
(20-40 disaccharide units
Proteoglycans
Glycoproteins
• Glycoproteins are proteins which have a central
protein chain linked oligosaccharide chains.
• Almost all human plasma proteins are glycoproteins
with the exception of albumin.
• Glycoproteins can contain more than 50% of
carbohydrates but generally the protein component
to prevail.
• 7 monosaccharides predominate in human
glycoproteins : Gal, Glc, Man, NeuAc, Fuc, GalNAc
and GlcNAc
GLYCOPROTEINS
Obrázek převzat z knihy: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005