2.9: Extracellular Matrix Flashcards
What forms the ECM (2)
Fibrillar and non-fibrillar components
What is the extracellular matrix
Complex network of proteins and carbohydrates filling space between cells
Fibrillar means
To produce fibres
Two roles of the ECM
-Architectural (structural role)
-Instructional (behaviours of the cell)
3 things ECM is essential for
- development
- tissue function
- organogenesis
3 key functions of ECM
-physical support
-determines mechanical and physiological properties of tissue
-influences growth, adhesion, differentiation status of cells and tissues
What mainly makes up the ECM
Connective tissue
3 Main components of the ECM
-collagens
-multi-adhesive glycoproteins
-proteoglycans
3 components making up basement membrane of ECM
- Type IV
- Laminins
- Perlecan
Properties of connective tissue in bone
Hard and dense
Properties of connective tissue in cartilage
Resilient and shock absorbing
Properties of connective tissue in tendons and skin
Tough and flexible
Reason behind various properties of connective tissues
- different types of collagen
- different arrangement of oriented collagen
What cell produces collagen
Fibroblasts
What is connective tissue made up of
ECM and component cells
3 proteoglycans
Aggrecan
Versican
Decorin
2 multi-adhesive glycoproteins
Fibronectin
Fibrinogen
What type of protein is collagen
Fibrous
How many different types of collagen are there in humans
28
Structure of each collagen molecule
Three a chains forming a triple helix
Chains in Type I collagen structure
3 chains from two different genes
What is a homotrimer
Collagen has one chain type
What types of collagen are homotrimers
Type II
Type III
What type of collagen is a heterotrimer
Type 1
What is commonly the x and y of the glycine-x-y repeat
X = proline
Y= hydroxyproline
What amino acid occupied every third position on in the alpha helix chain of collagen
Glycine
What property of aggrecan allows it to resist compressive forces as part of the cartilage?
High negative charge —>
High degrees of GAG sulfation with large numbers of negatively charged carboxyl groups attracts cations (Na+ ). large quantities of water retained by the highly negatively charged environment, resist compressive forces.
Under compressive load, water is given up by aggrecan, but regained once the load is reduced.
Which of the following are potential features of Marfan’s syndrome? (Due to Mutations in the protein fibrillin-1)
Predisposition to aortic ruptures
Why does the amino acid glycine feature so frequently in the primary sequence of a collagen chain?
Its small sidechain occupies the interior of the triple helix, allowing for tight packing
Composition of type 1 collagen
[a1(I)]2[a2(I)]
What provides tensile strength and stability in collagen?
Crosslinking
When does cross linking in collagen take place?
Following collagen secretion
What is an essential post translational modification which contributes to interchain H bond formation?
Hydroxylation of proline and lysine
What enzymes are required for the hydroxylation of lysine and proline
Lysyl hydroxylase
Prolyl
(require Fe2+ and Vit C)
What happens to collagen when you have a lack of Vit C (deficiency)
Collagen underhydroxylated
When does collagen cross linking occur
After fibril formation
2 fibril associated collagens
Type IX (9)
Type XII (12)
Function of fibril associated collagens
Regulate organisation of collagen fibrils
Type IV collagen characteristics (2)
- network-forming collagen
- in all basement membranes (structure varies from tissue to tissue)
Symptoms of Ehlers-Danlos syndrome
- stretch skin
- loose joints
Due to mutations affecting collagen prod. In connective tissue
How is tensile strength in collagen established?
Fibres held in parallel bundles resisting tensile force in one direction
What are collagen alpha chains synthesised from?
Pro-alpha chains (Longer precursors)
What is cleaved from procollagen to make collagen?
N-terminal and C-terminal propeptides
Where is type 4 collagen found
Basement membrane
What type of network does type 4 collagen from?
Sheet-like network
What happens to the N and C terminus in type 4 collagen?
Remains intact
Alternate name for basement membrane
Basal lamina
What is the basal lamina
- thin, flexible, mat of extra-cellular matrix which epithelial cell sheets sit on top of
3 structures basement membrane surrounds
- muscle
- peripheral nerve
- fat cells
How is the basement membrane involved in kidney ultrafiltration
Form the glomerular basement membrane
What is diabetes nephropathy?
Disorder where accumulation of ECM leads to highly thickened basement membrane
What is Alport Syndrome?
Mutations in Collagen IV
Result in abnormally laminated Glomerular basement membrane
Loss of kidney function and hearing loss
What helps decrease extent of electric fibres stretching?
Fibres interwoven with collagen
What are elastin fibres composed of?
Elastin protein core, surrounded by microfibrils (protein rich — fibrilin)
Amino acid covalently cross linked in elastin
Lysine
Where is fibrillin found
In microfibrils surrounding the elastin core
Mutations in Fibrillin-1 are associated with ______ syndrome
Marfans syndrome
Individuals with Marfans syndrome are more predisposed to….
Aortic ruptures
