Extra Cellular Matrix Flashcards
What is the Extracellular Matrix? What is it important for?
A three-dimensional network of extracellular macromolecules. Found in the space between cells in tissues. The ECM (Along with cell adhesion) is critical for the organisation, development, function, and dynamics of tissues.
What are the 2 extremes of animal tissue organisation? Describe them and their differences.
Epithelial Tissues: Sheets of tightly bound cells, cell-cell adhesions linked to cytoskeleton, have a thin layer of ECM. Mechanical stresses are transmitted from cell to cell.
Connective Tissues: Rich in ECM components (e.g. collagen fibres), have few cells and few cell-cell adhesions. Cell-matrix adhesions are important.
The ECM Directly bears mechanical stresses of tension and compression. The ECM determines the physical properties of connective tissues.
Types of Connective Tissue:
- Tendons:
- Bone:
- Cartilage:
- Blood Vessel Walls:
- Vitreous Content of the Eye:
ECM in different tissues is adapted to particular functional requirements.
Components of the ECM:
2 Main types of components:
- Glycosaminoglycan Polyacrylamide Chains (GAGs)
- Fibrous proteins:
- e.g. Collagen, Fibrillin, Elastin, Laminin
GAGs:
4 main groups:
- Hyaluronan
- Chondoitin Sulfate and Dermatan Sulfate
- Heparan Sulfate
- Keratan Sulfate
GAGs are unbranched polysaccharide chains composed of repeating disaccharide units, where one of the 2 sugars is always an amino sugar. The other sugar is usually a uronic acid (both carbonyl and carboxylic acid functional groups).
GAGs are highly negatively charged (due to sulfate and carboxyl groups)
Hyaluronan:
A GAG: A component of the ECM
Attracts water, creating pressure. Is a non-compressible space filler. Like other GAGs adopts highly extended conformation.
Proteoglycan:
A compound consisting of a protein bonded to mucopolysaccharide groups, especially present in connective tissue.
A single core protein can have variable numbers and types of GAGs
Examples of Proteoglycans: Aggrecan, Decorin, Betaglycan.
Collagen:
- The major fibrous component of the ECM.
- 25% of total protein mass of mammals (major component of skin and bone)
- Collagen fibrils provide tensile strength (resistance to stretch)
- Different combinations expressed in different tissues
- Some collagens form fibirls
- Collagen fibrils bundle into fibres
- Collagen alpha chains form trimers: Each chain folds into a helix with 3 AA’s per turn. They wrap tightly around each other to form a tightly packed trimer helical rod.
- Fibril-associated collagens don’t form fibrils but instead bind to the fibrils of fibrillar collagens, where they mediate fibril interactions with each other and with other ECM molecules to determine fibril organisation. e.g. Type XII binds to Type I fibrils in tendons.
Elastin:
- Fibrous component of the ECM.
- Elastic fibres provide resilience i.e. ability to recoil after stretch.
- Elastin is the main component of elastic fibres.
- Elastin is hydrophobic and is a highly crosslinked network of fibres and sheets.
Fibronectin:
- Fibrous component of the ECM.
- Helps attach cells to the ECM via binding with “integrins”.
The Basal Lamina:
- Very thin, tough, flexible sheet of ECM
- Connects the epidermis to the dermis.
- Lies beneath epithelia and surrounds muscle and nerve cells.
Function:
- Physical Support/ Scaffold For Cells
- Selective Cell Barrier
- Determines Cell Polarity, Survival, Function
Molecular structure of basal lamina:
- Laminin (A heterotrimer of alpha, beta, gamma chains)
- Integrin
- Perlecan
- Nidogen
- Type IV Collagen
Remodelling/degradation of the ECM:
The extracellular matrix is secreted and organised by cells within it:
- Remodelling occurs during wound healing/ bone remodelling/ normal tissue development etc.
- Remodelling is carried out by cellular proteases (matrix metalloproteases (MMPs) e.g. MMP-9 (collagenase), serine proteases e.g. Urokinase)
- Remodelling is actively confined to cells by inhibitors/local activation from inactive precursors/ cell surface localisation.
