The Extracellular Matrix Flashcards
Why is the ECM important?
- Architecture of natural tissues and organs
- Bioenginerring and synthestic organs
- Supports cells and affects mechanical properties
What is the ECM?
An extracellular assembly of glycoproteins, collagens, and polysaccharides
What are the 2 main forms of ECM?
- Connective tissue ECM
- Basement membrane
What are the major components of the connective tissue ECM?
- collagen based fibrils
- fibrillin and elastin microfibrils
- Fibronectin fibrils
- Extracellular proteoglycans
- Hyaluronan
What is the connective tissue ECM?
- 3D meshwork that surrounds mesenchymal cells or neurons
What do collagen fibres give the connective tissue ECM?
High tensile strength
What provides elasticity of connective tissue ECM?
Fibrillin
What are the features of fibrillar collagens?
- Globular N and C terminals
- Helical central domain with GXY repeats
- 3 polypeptide helices come together
What makes up mature collagen?
- Only the helix region
- N and C globular domains are cleaved
What kind of helix does the helical domain of GXY repeats form?
Left handed
What kind of helix do the 3 polypeptides of protocollage form?
Right handed
What are the features of fibrillin-1?
- Secreted protein with mnay EGF-like domains
- 7 TB domains
- Multimerises by crosslinks into micro-fibrils
- Many binding sites for other ECM proteins
What are the functions of fibrillin-1?
- Adds stretch/elasticity
- Binding sites for TGF-β growth factors and controls their localisation
In a relaxed state what kind of form is elastin in?
A disordered state
How is TGF-β bound to microfibrills?
As a large latent complex
What happens to elastin when it is elongated under mechanical force?
The simple molecular structure becomes highly crosslinked
How does TGF-β interact with microfibrils?
- Binds to microfibrills in latent complex
- Held in inactive state
- Under certain conditions TGF-β is released and can activate gene expression for cell survival
Under what conditions is TFG-β freed?
- Proteases produced
- Action of mechanical force on microfibrils
What causes Marfan’s syndrome?
Mutations in Fibrillin-1
What does Marfan’s syndrome affect?
- Microfibril organisation and strength
- Causes very flexible joints
- Progressive cardiovascular, skeletal, or occular problems
How does mutation in Fibrillin-1 cause the symptoms of Marfan’s syndrome?
- Results in aberrant local activation of TGF-β and excess TGF-β signalling
- TGF-β signalling regulates expression of ECM genes and ECM composition
- Due to microfibril disortion weakening TGF-β more likely to be released
