Extracellular Matrix Flashcards
What are the two types of ECM
Interstitial fluid and basement membrane
What macromolecules make up the ECM
Fibrous proteins (Collagen, elastin etc.)
Ground substance containing GAGs, proteoglycans, glycoproteins and aggregates
What are GAGs
Repeating chains of disaccharide sugar molecules
Describe the structure of a proteoglycan
A protein core with many GAGs branching off
What is the key attribute of proteoglycans + what function does it serve
Hydrophilic so they attract water creating a cushion which helps resist compressive forces
Examples of GAGs + Where are they found
Heparan Sulphate - Basement membrane
Hyaluronic acid - Synovial fluid + many other places
Keratan Sulphate - Cartilage
Chondroitin Sulphate - Cartilage
Examples of proteoglycans, location and what GAGs make them up
Aggrecan - Cartilage - Chondroitin + Keratan Sulphate
Perlecan - BM - Heparan Sulphate
Syndecan - Cartilage - Chondroitin + Heparan Sulphate
Decorin - Many connective tissues - Chondroitin + Dermatan Sulphate
What is an aggregate
Aggregates contain a hyaluronic acid backbone with many aggrecan proteoglycans branching off
Where are aggregates primarily found
Cartilage
Describe the structure of collagen
Three polypeptide alpha chains form a triple helix
Strands are made up of repeating Gly-X-Y amino acid sequence
What glycoprotein is required to assemble elastin fibres
Fibrillin
Types of collagen + where are they found
Type I - Dermis, bone, tendons, ligaments, fibrocartilage
Type II - Hyaline cartilage
Type III - Liver, granulation tissue, bone marrow, lymphoid organs
Type IV - Basement membrane
How does the structure of Type I and Type IV collagen differ
Type I features strong fibrous cords of collagen
Type IV Is a flat-like sheet
What is the basement membrane + where is it found
Tough, thin sheet of connective tissue separating epithelial and connective tissue
Functions of basement membrane
Prevent inwards growth of epithelial tumours
Supply nutrients to epithelial cells
Binding of different tissues
Maintains cell polarity and allows for cell signalling between tissues
What components of the ECM are found in the basement membrane
Type IV Collagen
Fibrillin
Heparan Sulphate
Examples of glycoproteins in the ECM + function
Fibrillin - Assembly of elastin
Fibronectin - Linker role in BM, organises ECM, cell attachment in BM
Laminin - Organiser of BM
What produces collagen
Fibroblasts
What are the cells in cartilage called
Chondrocytes
Types of cartilage + where is it found
Fibrous cartilage: Nose, pubic symphasis, between IV discs
Elastic cartilage: Epiglottis and ear
Hyaline cartilage: Covers joint surfaces
What components of the ECM are found in cartilage
Aggregates
Syndecan
Keratan sulphate, chondroitin sulphate
Type I or II Collagen
Functions of the ECM
Anchors cells through hemidesmosomes and focal adhesions
Strongly influences embryogenesis
Reservoir for growth factors and cell signals
Pathways for cell migration and attachment
Bears mechanical stress of tissue eg. in bone
What GAG doesn’t form a proteoglycan
Hyaluronic acid
When is normal ECM remodelling observed
Embryogenesis
Wound Repair
Angiogenesis
What proteins are primary involved in degrading the ECM
Elastase
Collagenases
Matrix Metalloproteinases
Proteases
When is abnormal ECM remodelling observed
Pathogens breaking through
Tumour migration
What are the three layers of the BM
Lamina Lucida
Lamina densa
Lamina fibroreticularis
What changes are observed in the basement membrane during diabetes mellitus
Thickening of BM in glomerulus changes cell permeability
What happens to the BM during Goodpasture’s Syndrome
Autoantibodies attack collagen IV destroying BM in glomerulus and lung
Cause of Marfan’s Syndrome
Mutation in fibrillin gene meaning elastin is not arranged correctly
Effect of Marfan’s Syndrome
Heart problems, impaired vision and incorrect limb arrangement/length
Cause of Ehlers-Danlos Syndrome
Mutations in collagen genes
Effect of Ehlers-Danlos Syndrome
Hypermobility and very stretchy skin
