Extracellular Matrix Flashcards
Cell Adhesion is crucial for the development of multicellular organisms
Blastocyst——->Developing embyro ——–> Tissue
ECM
Cells hold onto each other via junctional complexes
Cells hold onto the surrounding environment – the Extracellular matrix
Cell Biology Principle 1- Cells are always in motion
Microtubules organise movement in the cell interior
Actin microfilaments allow cells to move from one location to another
Intermediate filaments maintain cell structure and resist external forces caused by this movement
Principle 2
Cells within tissues are physically contiguous with their surroundings
Cells do not “float in space;” they are physically connected to specific structures in neighboring cells and the extracellular matrix (ECM):
Collagen
Fibronectin
Elastin
Proteoglycans
Laminins
Integrins
Cells adhere to the ECM via a receptor family known as Integrins.
ECM-integrin interactions
Cells make their own ECM and secrete it
Collagen provides structural support to tissues
Most abundant proteins in animal kingdom.
Can be bundled into fibres such as tendons, which can withstand enormous forces such as the strain imposed by muscle contraction on bone – tensile strength
Collagen structure underpins its strength
Several α chains—–>fibrils
Fibrils make——>fibres
Three polypeptide subunits (alpha proteins) wrapped in parallel to form a 300 nm-long coiled coil – often a heterotrimer.
Triple helical coiled-coil.
Characteristic repeat sequence consisting of glycine-X-Y.
These amino acids pack tightly together – facilitates coiled-coil formation
At least 29 proteins which can be mostly grouped into 4 classes.
Fibril Forming
Fibril Associated
Network Forming
Transmembrane
Fibril Forming
Bones, Cornea, Internal Organs, Ligaments, Skin and Tendons
Fibril Associated
Cartilage
Netwrok Forming
Basal Lamina
Transmembrane
Hemidesmosomes
Four classes of collagen structure
Fibrils joined together by other extracellular matrix proteins…including fibril-associated collagens (Facit).
Transmembrane and Network-forming
Four classes of collagen structure
Fibrils or ‘ropes’ – very strong along a single axis e.g. tendons.
Networks or ‘webs’ – can withstand stretching in multiple directions e.g. skin.
FACIT collagens – bind fibrils and networks together.
Transmembrane collagens – anchor cells to ECM e.g. hemidesmosome.
The Collagen ‘Assembly Line’
Intracellular trafficking through the secretory pathway – exocytosis.
Fibril assembly begins in fibripositors, and is completed in the extracellular space.
Medical importance of Collagen
Modification of procollagen to mature collagen is essential to form fibrils.
Procollagen peptidase (enzyme) requires vitamin C as a co-factor.
Lack of vitamin C (Scurvy) results in loss of structural support for tissues such as blood vessels, tendons, skin becomes fragile.
Mutations in the gene coding for alpha proteins cause disease – Osteogenesis Imperfecta or brittle bone disease.
Fibronectins Connect Cells to Collagenous Matrices
Fibronectin is the ‘glue’ that connects cells to collagen.
27 different proteins all from a single gene – alternative splicing.
Soluble and insoluble versions – the latter form fibres in ECM.
Continued
Contain 6 domains called ‘Fibronectin repeats’.
Classified into three groups—Type I, II, III.
Two fibronectin polypeptides are covalently linked via disulfide bonds at the C terminus.
Fibronectins contain domains called Fibronectin repeats
Some fibronectin repeats cause the peptide to bind to itself – inhibiting association with collagen until the dimer is outside of the cell.
Dimers are folded by interactions between type I and type III fibronectin repeats.
Pulling forces from actin-myosin network expose other binding regions
Formation of fibronectin fibres requires contact with the cell surface
Elastin Fibres Impart Flexibility to Tissues
Elastin is organised into elastic fibers:
Core region enriched in elastin proteins.
Hydrophobic and Hydrophilic regions.
Tough coating called microfibrillar sheath
Elastin Fibres permit tissue flexibility
Hydrophobic regions impart elasticity by clustering into coils under low stretch conditions.
Hydrophilic regions impart strength by forming covalent cross-links.
Like collagens and fibronectins – elastins are synthesised and secreted by cells.
Elastin molecules cross-link to one another by covalent bonds between lysines.
Elasticity is dependent on individual elastin molecules adopting alternative conformations – stretched or relaxed.
Tension in fibres cause elastins to take on an extended conformation, but they can ‘snap back’ upon relaxation.
