Tissues 3- Extracellular matrix biology 1 Flashcards
What is the extracellular matrix
A complex network of proteins and carbohydrates filling spaces between cells- deposited by cells, that becomes immobilised and fills the space between cells.
It comprises both fibrillar and non-fibrillar components
What are the functions of the extracellular matrix
Provides physical support
Determines the mechanical and physicochemcial properties of the tissue
Influences the growth, adhesion and differentiation status of the cells and tissues with which it interacts
Essential for development, tissue function and organogenesis.
Connective tissues are rich in ECM.
What is the basal lamina
A special type of ECM
What type of cells are embedded in the ECM
Macrophages and fibroplasts
Describe the components of connective tissues
All connective tissues contain a distinct spectrum of collagens, multi-adhesive glycoproteins and proteoglycans (extracellular matrix) together with a cellular component
Matrix components interact with specific cell surface receptors
Describe the types of collagen found in the ECM of connective tissues
Type I, II, III (fibrillar) Type IV (basement membrane)
Describe the types of multi-adhesive glycoproteins in the ECM of connective tissues
Fibronectin, Fibrinogen
Laminins (basement membrane)
Describe the types of proteoglycans found in the ECM of connective tissue
Proteoglycans
Aggrecan, Versican, Decorin
Perlecan (basement membrane
Describe some of the human disorders caused by ECM abnormalities due to gene mutations affecting matrix proteins
Gene mutations affecting matrix proteins
e.g. osteogenesis imperfecta - Type I collagen
Marfan’s syndrome - Fibrillin 1
Alport’s syndrome - Type IV collagen (5)
Epidermolysis Bullosa - Laminin 5 (in all 3 chains)
Congenital Muscular Dystrophy- Laminin 2 (2 chain
Describe some of the human disorders caused by ECM abnormalities due to gene mutations affecting ECM metabolism
e.g. Hurler’s syndrome - L--iduronidase
other “mucopolysaccharidoses” (inability to degrade GAGs)
Describe fibrotic disorders due to excessive ECM deposition
e.g. Liver fibrosis - cirrhosis
Kidney fibrosis - diabetic nephropathy
Lung fibrosis - silicosis
However, fibrosis can affect any organ.
Describe disorders due to the excessive loss of ECM
. Disorders due to excessive loss of ECM
e.g. osteoarthritis
Describe the varied properties of connective tissues
Tendon and skin: tough and flexible
Bone: hard and dense
Cartilage: resilient and shock-absorbing
Vitreous humour (jelly that fills interior of the eye): soft and transparent
Different types of collagen and arrangements of oriented collagen, as well as which other ECM components are present- different quantities of collagen too.
What are collagens
Family of fibrous proteins found in all multicellular organisms
Major proteins in bone, tendon and skin
Are the most abundant proteins in mammals, constituting 25% of total protein mass
How many different types of collagen are there
28 collagen types exist in humans, designated by roman numerals
There are 42 genes encoding collagens in humans
More genes- due to different alpha chains which make up collagen
Describe the molecular composition of collagen
Each collagen molecule comprises three chains, forming a triple helix.
Can be composed of one or more different chains
Type I collagen has chains from two different genes - its composition is [1(I)]2 [2(I)]
Types II and III collagen have only one chain type – their compositions are, therefore, [1(II)]3 and [1(III)]3
Describe the collagen triple helix
Characteristic gly-x-y repeat: x is often proline, y is often hydroxyproline
In fibrillar collagens, each chain is approximately 1000 amino acids, forming a left-handed helix
Why does the 3rd amino acid have to be glycine.
Three chains form a stiff triple helical structure – every third position must be occupied by glycine, as this is the only amino acid small enough to occupy the interior.
Describe the assembly of collagen into fibres
one chain
three chains
collagen fibril
collagen fiber
Describe collagen biosynthesis
Alpha chains are synthesised as longer precursors, pro-alpha chains, by ribosomes on the RER.
Inside the ER/Golgi Body- pro-alpha chains undergo a series of covalent modifications ( hydroxylation of selected prolines and lysines, glycolysations of selected hydroxylysines) to form triple-helical procollagen (N and C terminal polypeptides).
Secretion
Extracellular peptidases remove propeptides from procollagen- allowing collagen to associate laterally to form fibrils.
Cross-links to form fibres.
Describe lysine and proline hydroxylation
Prolyl and lysyl hydroxylases require Fe2+ and vitamin C
Contributes to interchain hydrogen bond formation.
Lysine and hydroxylysine are also modified in the formation of covalent crosslinkages. This takes place only after the collagen has been secreted.
Vitamin C-deficiency results in underhydroxylated collagens, with dramatic consequences for tissue stability (scurvy).
Describe the importance of the intermolecular covalent links
Provides tensile strength and stability. Both lysine and hydroxy-lysine residues are involved. The type and extent of cross-links is tissue specific and changes with age.
Gap regions- point of weakness- reduce length of these.
In how many directions do parallel bundles resist tensile forces
1- in tendons- collagen forms fibrils along the major axis of tension
Describe how collagen is arranged in the skin
The collagen fibres are arranged perpendicularly in one direction- to resist tensile stress in multiple directions. Fibroblasts work on the collagen they secrete, rearranging it into different arrangements, crawling over it and pulling on it to arrange it into different sheets.
