Extracellular Matrix Flashcards
What is the ECM?
Non-cellular compinent present within all tissues and organs
What are the types of ECM?
- Interstitial Connective Tissue Matrix; surrounds cells and provides structural scaffolding for tissues
- Basement membrane; seperates epithelium from surrounding stroma
Where may ECM be found?
- Bone
- Tendon
- Cartilage
- Cornea
- Blood vessel walls
- Dermal layer of skin
- Vitreous body of eye
-Basement Mmebrane
What are the functions of the ECM (insterstitial connective tissue matrix)?
- Provides mechanical and structural support
- Tensile strength
- Determines cellular microenvironment;
- anchors cells through cell-ECM junctions
- strongly influences embryonic development
- provides pathway for cellular migration
- establishes and maintains stem cell niches
What are the components of Interstitial connective tissue ECM?
Fibres- Collagen, Elastin
Ground Substance-
Proteoglycans, glycosaminoglycans, glycoproteins
What is the structure of collagen?
3 collagen polypeptides form a triple helix
What stain can be used to see elastin?
Van giesen stain
What does assembly of elastin into functional fibres require?
Presence of glycoprotein-fibrillin.
How is ECM arranged in connective tissue?
Can differ:
-Loose irregular connective tissue- lymphoid tissue
-Dense irregular connective tissue- dermis
OR SPECIALISED
-dense regular (tendons and ligaments)
-bone
-cartilage
How are ECM fibres synthesised?
Collagen is synthesised as procollagen and post translational modifications glycosylation and hydroxylation form collagen.
Elastin is synthesised as tropelastin and post translation modification hydroxylation forms elastin.
How are proteoglycans synthesised?
Core protein synthesised on rER.
Addition of polysaccharide as disaccharide repeats in golgi.
Delivered to extracellular compartment by exocytosis.
Assembly with other ECM components.
What is ground substance?
- An amorphous, colourless, gelatinous material.
- Fills the spaces between fibres and cells.
- Consists of large molecules called glycosaminoglycans which link with a core protein to form proteoglycans.
- Very good at absorbing water, allowing it to be resistant to compressive forces.
What are glycosaminoglycans (GAG’s)?
- Chains of repeating disaccharide units
- Extremely hydrophillic
- Enables matrices to withstand high compressive forces.
What are examples of GAG’s in cartilage?
- Chondroitin sulfate
- Keratan sulfate
What is basement membrane ECM composed of?
Composed of:
- collagen IV
- laminin
- nidogen
- perlecan
What are some of the features of basement membrane ECM?
- A thin, tough sheet of ECM
- Mat like arrangement
- Can surround cells
- Can separate 2 sheets of cells eg. glomerulus in kidney
What are the functions of basement membrane ECM?
- Support
- Path for cell migration
- Barrier to downward growth
- Permits flow of nutrients
- determines cell polarity
- binding to underlying connective tissue
- mediates signals between cells and connective tissue
What are proteoglycans?
-Is a protein core + GAG’s
What are examples of proteoglycans in the cartilage?
- Aggrecan; GAG’s: -keratan sulfate, chondroitin sulfate
- Syndecan; GAG’s:-chondroitin sulfate, heparan sulfate
What are the other structural glycoproteins involved in ECM ground substance?
- Fibrillin; controls deposition and orientation of elastin
- Fibroconectin; linker role in basement membrane, organises ECM and participates in cell attatchment to BM.
- Laminin; Primary organiser of BM layer
What are some disorders involved in the basement membrane?
- Cancer= epithelial tumours regarded as malignant once BM is breached
- Diabetes Mellitus= Thickening of BM in glomerulus changes permeability.
- Epidermis Bullosa= attatchment of epidermis to BM
- Goodpastures syndrome= Autoantibodies to collagen IV destroy BM in lung and glomerulus.
How is the ECM in bone arranged?
The bone has an acellular and cellular part.
Acellular=ECM
Acellular part has organic and inorganic parts.
Inorganic part is hydroxyapatite (calcium salts)
Organic part is type 1 collagen and osteocalcin
What is the cellular part of bone?
- Osteoblasts; synthesise osteoid
- Osteoclasts; degrade osteoid
- Osteocyte; used for maintenance
What are the types of cartilage?
- Hyaline
- Articular
- Elastic
- Fibrocartilage
What is cartilage synthesised by?
By chondrocytes
What are some molecules that are in cartilage?
- Type II collagen
- Chondroitin sulfate
- Keratan sulfate
- hyaluronic acid+aggrecan to help attract H2O
What can happen when the ECM goes wrong?
- Over degradation could lead to osteoarthritis
- Over production could lead to fibrosis
What are specific conditions that could occur as a result of defected components in ECM?
- Elastin; Supraclavicular Aortic Stenosis
- Fibrillin 1; Marfan Syndrome
- Collagen 1; Ehlers-Danlos Syndrome
- Collagen IV; Alports Syndrome
What are the consequences of deregulated ECM remodelling?
- ECM synthesis; hyperproliferation of fibroblasts; excess ECM, can lead to Fibrosis, Embryogenesis, Angiogenesis
- Pathogens may secrete collagenase and allow invasion of host by bacteria
- Excess activation can mean MMP’s are made and allow tumour cell invasion