What is the extracellular matrix (ECM)?
The non-cellular component present within all tissues and organs
It is a 3D macromolecular network that supports processes from local tissue growth to organ maintenance.
Name the two key types of ECM.
- Interstitial Matrix
- Pericellular Matrix
Interstitial Matrix surrounds cells, while Pericellular Matrix, such as the Basement Membrane, separates epithelium from the surrounding stroma.
What are the functions of the ECM?
- Provides mechanical and structural support
- Tensile strength
- Determines cellular microenvironment
- Anchors cells
- Influences embryonic development
- Provides pathways for cellular migration
- Sequesters growth factors
- Provides a residence for phagocytic cells
- Establishes and maintains stem cell niches
These functions are crucial for tissue integrity and cellular behavior.
What are the major components of the ECM?
- Fibrous proteins (Collagens, Elastin)
- Ground Substance (Noncollagenous glycoproteins, Glycosaminoglycans, Proteoglycans)
These components contribute to the structural and functional properties of the ECM.
What is the composition of collagen?
30% of total protein mass of the body; 28 types in vertebrates; structural motif - triple helix
Collagen molecules are comprised of repeating 3 amino acid motifs forming α-chains.
What are the types of collagen and their locations?
- Type I: Skin, tendon, bone, heart, ligaments
- Type II: Cartilage, developing cornea, vitreous humour
- Type III: Loose connective tissues, lung, vascular system
- Type IV: Basement Membrane of epithelia, muscle
Types I and II are fibrillar; Type IV is sheet-forming.
What is the role of elastin in the ECM?
Provides flexibility required for function of blood vessels, lungs, and skin
Elastin is the primary protein of elastic fibres and is rich in Glycine and Proline residues.
What are glycosaminoglycans (GAGs)?
Linear unbranched oligosaccharides that covalently bond to protein core to form Proteoglycans
GAGs are hydrophilic and aid in compression resistance.
List the locations of different GAGs.
- Hyaluronic Acid: Joints and ocular fluids
- Chondroitin Sulphate: Cartilage, tendons, bone, heart valves
- Dermatan Sulphate: Skin, heart valves, blood vessels
- Heparan Sulphate: Cell surfaces and basement membranes
- Heparin: Mast cells and basophils
- Keratan Sulphates: Cartilage, cornea, bone
GAGs have tissue-specific distribution.
What are proteoglycans?
GAGs + Protein Core; primarily provide structural support to tissues
Aggrecan is a large aggregate of chondroitin sulphate and keratan sulphate chains associated with hyaluronic acid.
What is the basement membrane?
Thin, tough, flexible sheet of matrix components underpinning all epithelia
Functions include anchoring cells to connective tissues and filtration.
How is collagen synthesized?
Primarily synthesized by fibroblasts; α-chains synthesized in RER as preprocollagen
Procollagen undergoes modifications and is transported to the Golgi apparatus.
What is the process of elastin synthesis?
Synthesized by fibroblasts and smooth muscle cells; initially as monomeric tropoelastin
Cross-links form between fibres in the extracellular space.
What is the ECM’s role in remodelling?
Constant state of deposition, degradation, repair, and remodelling; mediated by matrix metalloproteinases (MMPs)
MMPs can be membrane-bound or free in the extracellular space.
What are specialized connective tissues?
- Bone
- Cartilage
- Adipose Tissue
- Blood
- Bone Marrow
- Lymphoid Tissue
These tissues have unique ECM compositions and functions.
What is the composition of bone?
Dense, rigid matrix of organic (30% - type I collagen, osteocalcin) and inorganic (70% - Hydroxyapatite) substances
Bone is continually remodelled by osteoblasts and osteoclasts.
What are the three major types of cartilage?
- Hyaline cartilage
- Fibrocartilage
- Elastic cartilage
Each type has distinct structural features and locations.
What is Osteogenesis Imperfecta?
Congenital condition caused by defects in type I collagen synthesis; symptoms include frequent bone fractures
Management includes bisphosphonate drugs.
What is Marfan Syndrome?
Caused by mutations in FBN1 gene; disrupts proper assembly of elastic fibres
Symptoms include tall stature, arachnodactyly, and cardiac abnormalities.
What is Ehlers-Danlos Syndrome?
Characterized by joint hypermobility, skin hyperextensibility, and tissue fragility
Treatment is specific to the subtype and may involve genetic counselling.
What is Goodpasture Syndrome?
Autoimmune disease caused by autoreactive antibodies to α-3 chain of type IV collagen; affects renal and pulmonary function
Symptoms include glomerulonephritis and pulmonary haemorrhage.
