ECM

ECM

1. Part of tissue that:

   • Sequesters water – turgor for soft tissue
   • Sequesters minerals – rigidity for bone
   • Substrate for cell adhesion
   • Reservoir for growth factors – reg proliferation, movement, differentiation of cells within it

2. Tissue repair depends on growth factor activity and interaction between cells and ECM components

3. Interstitial matrix

   • Spaces between cells in CT, between EP – Between EP and supportive vascular and SM tissue
   • Forms 3D amorphous gel
   • Constituents
     • Collagen (fibrilar/non-fibrilar
     • Fibronectin
     • Elastin
     • Hyaluronan

4. Basement membrane

   • CT between EN and everything else below it
   • Highly organised around EP and EN = specialised BM
   • Synthesized by EP (above) and mesenchymal cells (below)
   • Constituents
     • Collagen (non-fibrilar)
     • Laminin
     • Proteoglycan

5. Role

   • 1. Mechanical support – cell adhesion, migration
   • 2. Control cell growth – components regulate proliferation
   • 3. Maintain cell differentiation – ECM proteins affect degree of differentiation
   • 4. Scaffolding for tissue renewal – integrity of BM critical for organised tissue regeneration
   • IF ECM damaged > collagen deposition and scar formation

6. Components

   • Fibrous structural proteins
     • Strength and recoil
     • Collagen – Fibrilar (cross-linking giving tensile strength), Non-fibrilar (BM, IV discs)
     • Elastin – recoil and return to base structure after stress (BV, uterus, skin, ligaments)
   • Water hydrated cells
     • Turgor > resilience and lubrication
     • Proteoglycans – hydrated compressible cells give resilience and lubrication (cartilage and joints)
     • Hyaluronan – Able to bind water forming viscous gel-like matrix adding to compresability of tissue (reservoir for GF)
   • Adhesive glycoproteins
     • Adhesion between Cell-Cell, Cell-ECM, ECM-Components
     • Fibronectin – Binds to many ECM components, Tissue (aggregates at wound sites), Plasma (binds to fibrin during clot formation and for re-EP)
     • Laminin – Cell to underlying components mediating attachment to BM
     • Integrins – transmembrane glycoproteins, main receptors for ECM components connecting intra and extracellular environemnts

7. GENETIC DEFECTS

   • Osteogenesis imperfecta
     • Collagen defect – Brittle bone disease
     • Defective collagen gene leading to formation of abnormally fragile bones
     • Defects in eyes d/t insufficient deposits (blue sclera)
     • Lax ligaments – dislocations
     • Teeth - weak and brittle
     • Otosclerosis – tympanic membrane and earbones become hard and fused
   • Ehlers-Danlos syndrome
     • Skin – very elastic with retraction, but not enough colagen to give strenth, vulnerable to trauma
     • Genetic disorder affecting collagen in CT
     • Joints – hypermobile, dislocate easily
     • Corneal detachment – not enough collagen in cornea
     • Diaphragmatic hernia
     • Rupture of large arteries (aorta, femoral, carotid) and colon
   • Marfan syndrome
     • Genetic defect of fibrillin resulting in structural loss of CT
     • Tall growth with arachnodactily
     • Indented breastbone (affects respiration/heart)
     • Aorta – prolapsed valves, dissection, aneurism

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