Cell Bio- Extracellular Matrix And Cell Junctions

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What is extracellular matrix:

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A system of protein and polysaccharide molecules which fill the intercellular space

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Two main types of macromolecules form the extracellular matrix:

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- Fibrous proteins
- Polysaccharide
- Glycosaminoglycans

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Function of extracellular matrix:

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Fill the intercellular space and thus it is responsible for mechanical and other physical properties of the tissue (bone, cornea, tendon)
- ECM is very important for the structure and properties of connective tissue

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Cell types of the connective tissue producing ECM:

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- Fibroblasts (most connective tissues)
- Chondroblast (cartilage)
- Osteoblast (bone)

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Fibrous proteins of ECM:

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1. Collagens
2. Elastin
3. Fibronectin
4. Laminin

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Collagens:

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- 3 polypeptide chains of collagen form triple helixes which form polymeric fibrils (10- 300nm)
- Collagen fibrils assosiate and form collagen fibers (0,5- 3 micrometers)
- Collagen contains amino- acids hydroxylysine and hydroxiproline (after translation)
- Collagen is synthesized as procollagen
- Collagenase cleaves terminal domains of procollagen when it is secreted to the EC- space-- > polymerization and aggregation
- Collagens are the main proteins in skin, tendon and bone (most abundant protein in the body 25%)
- Collagen fibers goes in different directions making it very resistent

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Elastin:

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- Covalently crosslinked fibrous molecules of elastin form elastin fibers
- Elastin fibers have rubber - like properties. Can be stretched and have great resistance.
- Main protein in arteries

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Fibronectin:

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Dimer which binds to other components of extracellular matrix (e.g. collagen)

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Laminin:

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Trimer forming a cross which together with type IV collagen represent the main components of basal lamina. (Not the same as protein "Lamin")

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Polysaccharide of ECM:

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Glycosaminoglycans (GAGs). Often covalently linked to proteins and thus they form proteoglycans (most sugar, less protein)

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GAGs:

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- Unbranched polysaccharides made of repeated disaccharide units.
- One of the saccharides is an amino- sugar (e.g. N- acetylglucosamin) which is often sulphated (bond) and the second saccharide is an uronic acid.

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Main type of GAGs:

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1. Hyaluronan
2. Chondroitin sulphate
3. Heparan sulphate
4. Keratan sulphate

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Proteoglycans:

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- Polysaccharide fibers are attached to the core protein.
- Can aggregate with GAGs and thus they form huge aggregates (aggrecan aggregate in cartilage)
- Proteoglycan form gels and they are responsible for mechanical properties of tissue

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What are cell junctions?

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Protein structures which are responsible for connection of the cell with other cells or connection of the cell with ECM

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Function of cell junctions:

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1. Mechanical connection of cells
2. Attachment of cells to ECM
3. Communication between cells

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Cell junctions are important in organizing tissues. Functional types of cell junctions:

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1. Occluding cell junctions
2. Anchoring cell junctions
3. Communicating cell junctions

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Occluding cell junctions:

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- They seal the space between neighboring cells and thus even solubilized molecules cannot pass through this space
- Tight junctions: are made of proteins claudins and ocludins. Are responsible for the selective permeability of epithelial cells. In the intestine transport of substances is realized via the cells of intestinal epithelia and not via the space between the cells.

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Anchoring cell junctions:

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They attach cells and their cytoskeletons to neighboring cells or to the ECM.
Types of anchoring cell junctions:
1. Junctions bound to microfilaments
2. Junctions bound to intermediate filaments

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Junctions bound to microfilaments (made of actin protein):

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- Adherens junctions: they mediate the connection of microfilaments of neighboring cells via transmembrane proteins cadherins. In epithelial cells, they are located just below tight junctions.
- Focal adhesions: mediate the connection of microfilaments of cells with the ECM via transmembrane proteins integrins. Actin of microfilaments is attached to integrins via proteins vinculin, alpha actinin, talin, filamin.
- Adhesion belt: (zonula adherend) just below the tight junctions, continuos and encircling each cell

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Junctions bound to intermediate filaments:

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1. Desmosomes
2. Hemidesmosomes

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GAGs:

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- Unbranched polysaccharides made of repeated disaccharide units.
- One of the saccharides is an amino- sugar (e.g. N- acetylglucosamin) which is often sulphated (bond) and the second saccharide is an uronic acid.

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Main type of GAGs:

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1. Hyaluronan
2. Chondroitin sulphate
3. Heparan sulphate
4. Keratan sulphate

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Proteoglycans:

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- Polysaccharide fibers are attached to the core protein.
- Can aggregate with GAGs and thus they form huge aggregates (aggrecan aggregate in cartilage)
- Proteoglycan form gels and they are responsible for mechanical properties of tissue

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What are cell junctions?

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Protein structures which are responsible for connection of the cell with other cells or connection of the cell with ECM

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Function of cell junctions:

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1. Mechanical connection of cells
2. Attachment of cells to ECM
3. Communication between cells

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Desmosomes:

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- Mediate connections of intermediate filaments via transmembrane protein cadherins
- Responsible for mechanical resistance of tissue together with intermediate filaments
- Keratin in epithel, desmin in heart muscle cells
- Cytoplasmic plaque: intracellular anchor proteins (plakoglobin and desmoplakin)

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Hemidesmosomes:

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- Mediate connection of intermediate filaments with ECM via integrins.
- In epithelial cells they mediate the connection of keratin intermediate filaments with basal lamina (protein laminin) Intracellular anchor protein (plectin)

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Communicating cell junctions:

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- Gap junctions
- They enable direct transmission of chemical and electrical signals between neighboring cells

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Gap junctions:

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- Conexons: mediate connection between cytoplasm of twoo neighboring cells.
- Connexons are anchored in the plasma membrane of neighboring cells
- Connexon is composed of 6 parallel molecules of protein connexin forming a tube-
- Enables passage of small molecules (1000 Daltons) (cAMP, ions, NO proteins)--> enables metabolic and signaling interconnection of cells.
- Opening regulated by calcium

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Plasmodesmata and transient cell- cell adhesions:

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- Plasmodesma: plants only
- Transient cell- cell adhesions: Selectins: cell surface saccharide- binding proteins