Extracellular Matrix Flashcards
What is the extracellular matrix?
Extracellular matrix (ECM) is a complex network of macromolecules (proteins and carbohydrates) deposited by cells, made up of both fibrillar and non-fibrillar components. After being deposited, it becomes immobilized outside the cells and it fills in the spaces between cells.
What is ECM essential for?
Development, Tissue function, Organogenesis. ECM plays both architectural (mechanical stability) and instructional roles (influences cell behaviour). Key functions of the ECM are: 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.
What do connective tissues contain?
Connective tissues are particularly rich in extracellular matrix. All connective tissues contain a complex spectrum of collagens, multiadhesive glycoproteins and proteoglycans (extracellular matrix) together with a cellular component.
What are the varieties of extracellular matrix components?
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)
How is connective tissues with various properties generated?
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.
What is collagen?
These are a family of fibrous proteins found in all multicellular organisms. They are the most abundant proteins in mammals, constituting up to 25% of the total protein mass. Collagens are the major protein components of bone, tendon and skin, with at least 28 different collagen types existing in humans, denoted by Roman numerals. The different collagen components are encoded by 48 different genes.
What is each collagen molecule made of?
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.
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.
Describe hydrogen bond formation between collagen molecules
Just as proline undergoes a post-translational modification of hydroxylation, lysine and hydroxylysine are similarly modified in the formation of covalent cross linkages. This contributes to interchain hydrogen bond formation. hese provide tensile strength and stability. Both lysine and hydroxy-lysine residues are involved. Crosslinking only takes place only after the collagen has been secreted.
What is the impact of a vitamin C deficiency?
Vitamin C-deficiency results in underhydroxylated collagens, with dramatic consequences for tissue stability (scurvy). This is due to the enzymes prolyl hydroxylase and lysyl hydroxylase requiring vitamin C as a co-factor for functionality.
How does collagen biosynthesis work?
Collagen biosynthesis and secretion follows the normal pathway for a secreted protein. However, the collagen α chains are synthesised as longer precursors, called pro-α chains, by ribosomes attached to the endoplasmic reticulum. The pro-α chains undergo a series of covalent modifications and fold into triple-helical procollagen molecules, before their release from cells.
What are the steps in collagen biosynthesis?
Pro-a chains in ER Procollagen Cleavage of propeptide Collagen Fibril formation Cross linking
How are fibrils formed and what is their purpose?
Some collagens are fibril-associated and regulate the organisation of collagen fibrils in tissues. Staggered arrays of tropocollagen molecules form fibrils, which ultimately arrange to form collagen fibres. Tensile strength is provided by the fibres being in parallel bundles - these resist tensile force in one direction.
What is Ehlers–Danlos syndromes?
Group of inherited connective tissue disorders whose symptoms include stretchy skin and loose joints. Several of these can arise due to mutations in collagen, which negatively affect collagen production, collagen structure or collagen processing.
What are non-fibril forming collagens?
Not all collagens form fibrils. An important non-fibrillar collagen is the network forming collagen type IV, which is present in all basement membranes. In the collagen IV network, the collagen type IV molecules can associate laterally between triple-helical segments as well as head-to head and tail-to tail between the globular domains to give dimers, tetramers and higher order complexes.
What are basement membranes?
These are flexible, thin mats of extracellular matrix underlying epithelial sheets and tubes. Basement membranes surround muscle, peripheral nerve and fat cells and underlie most epithelia. They are highly specialized extracellular matrices containing a distinct repertoire of collagens, glycoproteins and proteoglycans.
