Composition and structure of connective tissue Flashcards
Give 3 examples of functions of connective tissue?
Mechanical support
Assist movement
Site of immune response
Do connective tissues contain neurovascular structures?
Yes
What are the 3 main components of connective tissue?
Cells
Structural components (in ECM)
Matricellular proteins (in ECM)
What is the function of cells in connective tissue, and give 3 examples of body structures that contain connective tissue and the associated cells?
Cells synthesise and breakdown connective tissue
Fibroblasts in skin and tendon ligaments
Chondrocytes in cartilage
Osteocytes, osteoblasts, osteoclasts in bone
What is the main function of structural components in connective tissue?
Provide mechanical properties by providing ground substance
What is ground substance, that composes structural components of connective tissue?
Amorphous/shapeless gelatinous material that contains all ECM components except from fibrous materials
What 3 substances make up the ground substance in the structural components of connective tissue?
proteoglycan predominantly, elastic and collagen fibres
Describe the structure of a proteoglycan?
Protein core coated by sugar-based polymers called glycosaminoglycans/GAGs/glycans
Different kinds of glycans which are built from different building blocks
Give 4 examples of properties of proteoglycans?
size variation ranges from 40dKa to over 100dKa
hydrophilic so allow water to be held in tissues
viscoelastic
interaction with cells, collagen and cytokines
What is aggrecan, and how does it form aggregate?
Aggrecans are proteoglycans that cluster with hyaluronan and link proteins to form a huge multimeric (protein composed of subunits) aggregate
Aggregate is a ball-shaped structures that give cartilage resistance to compression in cartilage
What is the function of link proteins in aggregate?
Link proteins stabilise binding of aggrecans to hyaluronan backbone
What structure coating aggregate makes it hydrophilic, and what property does this give the connective tissue overall?
Hydrophilic sulfated chondroitin-keratin sulphate complex chains of aggregates draw water into tissue which allows resistance to compression
In OA, how are aggregates and type 2 collagen fibres affected?
In OA, aggrecan and type II collagen are degraded by proteolytic enzymes which impairs mechanical properties of cartilage, causing joint pain
Do matricellular proteins have regulatory or structural roles?
Regulatory
In elastic fibres, what is the diameter of the microfibrils that compose them?
10nm
What 4 body structures contain elastic fibres so that they can stretch?
blood vessel walls, alveoli, bladder, tendons
What do elastic fibres target and activate?
Growth factors, especially TGF-beta
What 4 proteins compose elastic fibres?
elastin
fibrillin 1,2,3 proteins
fibulin 4,5 proteins
matrix-associated glycoproteins
Describe the composition and arrangement of elastic fibres in tendons?
In tendons, elastic fibres composed by long microfibrils and sit between collagen fibre bundles
What is the main matricellular protein and structural component of connective tissue?
Type 1,2,3 collagen fibres
How many types of collagen are there, and how many genes are these expressed by?
27 collagens that are expressed by 42 genes
What is each collagen molecule in a collagen fibril composed of, and how many genes are expressed to produce these?
Collagen fibrils are composed of many collagen molecules, with each molecule consisting of triple helix alpha polypeptide chains
each chain is a single gene product
What is the amino acid sequence of an alpha polypeptide chain which makes up collagen fibrils?
Glycine-X-Y repeats, where X is usually proline and Y is usually hydroxyproline (unusual AA that is mostly found in collagen)
What part of the amino acid sequence of alpha polypeptide chains allows them to intertwine and form a triple helix alpha polypeptide molecule?
Glycine is every 3rd residue in the amino acid sequence
What 2 properties do proline and hydroxyproline give collagen?
Rigidity, stability
Describe the turnover rate of collagen fibres?
Very slow turnover rate, so collagen is very stable
What percentage of the whole-body protein content is made up by collagen fibres?
12-17%
What is a homotrimer collagen and give one example?
Protein composed of 3 identical alpha polypeptide chains
eg. Type 2 collagen
What is a heterotrimer collagen and give one example
Protein composed of 2 or more different alpha polypeptide chains
eg. Type 1 collagen in skin and bone has 2 identical alpha chains and 1 different alpha chain
In collagen fibril synthesis, what occurs after alpha polypeptide chain translation?
Post-translational modification at RER of alpha polypeptide chain:
proline and lysine hydroxylation (vitamin C/ascorbate is cofactor)
hydroxylysine glycosylation
In collagen fibril synthesis, after the 3 alpha polypeptide chains have been modified how do they assemble into the triple helix alpha polypeptide molecules, and what is the name of this molecule?
3 modified alpha polypeptide chains form disulfide bonds between them to intertwine tightly and produce triple helix alpha polypeptide molecule which is called procollagen
In collagen synthesis, what happens to procollagen after it is produced in the cell?
Procollagen secreted from cell by exocytosis and enters ECM
In collagen fibril synthesis, how is procollagen converted into tropocollagen?
In ECM, N and C proteinases cleave N and C propeptides from procollagen, converting it to tropocollagen
In collagen fibril synthesis, how do tropocollagen molecules from a collagen fibril, and what enzyme catalyses this step?
Tropocollagen molecules assemble into collagen fibrils, then lysyl oxidase forms covalent cross-linkages between the molecules
How can vitamin C deficiency affect the strength of collagen fibrils, and what is the resulting condition?
Vitamin C deficiency reduces hydroxylation of proline and lysine, which weakens triple helix structure of procollagen, overall weaker collagen fibrils are formed and this presents as scurvy
Give 5 symptoms of scurvy?
Gum bleeding, teeth loss, skin lesions and bruising, joint pain and weakness, poor wound healing
Do all connective tissues have the same composition and organisation of collagen?
Different types of connective tissues have varying compositions and organisations of collagen
What is the primary protein component in bone, and how is it organised?
Primary protein component is type 1 collagen fibres which are arranged into concentric circular structures called lamellae
In tendons, how does collagen provide high tensile strength?
Parallel type 1 collagen fibre bundles provide tensile strength
In enthesis, do the proportions of collagen remain constant throughout its length?
No, enthesis structure varies along it length due to different collagen proportions
Why is the enthesis a common site of tendon pathology, and give 2 examples?
Mechanical stress is concentrated here, so microdamage and overuse injuries often occur
Give 5 examples of tendinopathy changes to collagen proportions and organisation?
Disorganised collagen fibrils
reduced fibril diameter
increased collagen turnover leads to higher proportion of type 3 collagen fibres
neurovascular infiltration which causes pain
failure to repair
In skin and blood vessels, what type of collagen forms the collagen fibrils?
Mixed fibrils formed from type 1,3 collagen
What kind of deficiencies can cause conditions with fragile skin and blood vessels?
Fragility occurs due to impaired collagen fibril formation from deficiencies in type 3 collagen (expressed by COL3A1 gene) which can lead to conditions such as Ehlers Danlos syndrome type IV
What percentages of types 1 and 3 collagen make up skin and blood vessels?
~60% type 1 collagen
~30% type 3 collagen
