Extracellular matrix Flashcards
Extracellular matrix (ECM)
complex network of macromolecules (proteins and carbohydrates) deposited by cells, made up of both fibrillar and non-fibrillar components.
After being deposited, it becomes immobilised outside the cells and it fills in the spaces between cells.
ECM Is essential for
- Development
- Tissue function
- Organogenesis (generation of organs)
ECM plays both roles
ECM plays both architectural (mechanical stability) and instructional roles (influences cell behaviour).
Key functions of the ECM are to:
- Provide physical support
- Determine the mechanical and physicochemcial properties of the tissue
- Influence the growth, adhesion and differentiation status of the cells and tissues with which it interacts.
Connective tissues
Connective tissues are particularly rich in extracellular matrix. Components of connective tissue: notably cells and extracellular matrix components.
All connective tissues contain a complex spectrum of collagens, multiadhesive glycoproteins and proteoglycans (extracellular matrix) together with a cellular component.
Many varieties of extracellular matrix component exist:
- Collagens - e.g. Type I, II, III (fibrillar), Type IV (basement membrane).
- Multi-adhesive glycoproteins - e.g. Fibronectin, Fibrinogen, Laminins (basement membrane).
- Proteoglycans - e.g. Aggrecan, Versican, Decorin, Perlecan (basement membrane).
Each matrix component is able to interact with the cellular components via specific cell surface receptors.
Diagram
Different types of connnective tissues have varied properties
Different types of collagen and different arrangements of oriented collagen, coupled with the presence or absence of different ECM components, generates a wide variety of connective tissues with the varied properties required for function.
eg the vitreous humour (the jelly that fills the interior of the eye) needs to be relatively soft and transparent.
Compare those properties with the other connective tissues shown below:
Human disorders resulting from ECM abnormalities
- Gene mutations affecting matrix proteins
Osteogenesis imperfecta - Type I collagen
Marfan’s syndrome - Fibrillin 1
Alport’s syndrome - Type IV collagen (a5)
Epidermolysis Bullosa - Laminin 5 (in all 3 chains)
Congenital Muscular Dystrophy - Laminin 2 (a2 chain)
- Gene mutations affecting ECM catabolism
a. k.a. mucopolysaccharidoses (MPSs) , inability to degrade GAGs)
Hurler’s syndrome - L-a-iduronidase
- Fibrotic disorders due to excessive ECM deposition
Liver fibrosis - cirrhosis
Kidney fibrosis - diabetic nephropathy
Lung fibrosis - idiopathic pulmonary fibrosis (IPF)
- Disorders due to excessive loss of ECM
e. g. osteoarthritis
Collagens
- These are a family of fibrous proteins found in all multicellular organisms.
- Most abundant proteins in mammals, constituting up to 25% of the total protein mass.
- Major protein components of bone, tendon and skin, denoted by Roman numerals. The different collagen components are encoded by 48 different genes.
- Each collagen molecule is made up of three α chains and can be a homotrimer or a heterotrimer.
- Type I collagen has chains from two genes. It is a heterotrimer with the composition [α1(I)]2 [α2(I)]
- Types II and III collagen are homotrimers, having only one chain type. Their compositions are therefore, [α1(II)]3 and [α1(III)]3
Skin collagen arrangements
Skin: successive layers at right angles to each other
Fibrils go in different direction - resisting tensile force in all directions
Mature bone and cornea : same arrangement
The collagen triple helix
The α chains form a triple helix. In fibrillar collagens, each α chain is approximately 1000 amino acids long, forming a left-handed helix.
The primary sequence of collagen proteins contains a characteristic glycine-x-y repeat where x is often proline and y is often hydroxyproline.
To form a stiff triple helical structure, every third position in the must be occupied by the amino acid glycine, as this is the only amino acid small enough to occupy the interior (H side chain)
