Extracellular Matrix

Question 1

Cell Adhesion is crucial for the development of multicellular organisms

Answer 1

Blastocyst——->Developing embyro ——–> Tissue

Question 2

ECM

Answer 2

Cells hold onto each other via junctional complexes
Cells hold onto the surrounding environment – the Extracellular matrix

Question 3

Cell Biology Principle 1- Cells are always in motion

Answer 3

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

Question 4

Principle 2

Answer 4

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

Question 5

Integrins

Answer 5

Cells adhere to the ECM via a receptor family known as Integrins.

Question 6

ECM-integrin interactions

Answer 6

Cells make their own ECM and secrete it

Question 7

Collagen provides structural support to tissues

Answer 7

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

Question 8

Collagen structure underpins its strength

Answer 8

Several α chains—–>fibrils
Fibrils make——>fibres

Question 9

Three polypeptide subunits (alpha proteins) wrapped in parallel to form a 300 nm-long coiled coil – often a heterotrimer.

Answer 9

Triple helical coiled-coil.

Characteristic repeat sequence consisting of glycine-X-Y.

These amino acids pack tightly together – facilitates coiled-coil formation

Question 10

At least 29 proteins which can be mostly grouped into 4 classes.

Answer 10

Fibril Forming
Fibril Associated
Network Forming
Transmembrane

Question 11

Fibril Forming

Answer 11

Bones, Cornea, Internal Organs, Ligaments, Skin and Tendons

Question 12

Fibril Associated

Answer 12

Cartilage

Question 13

Netwrok Forming

Answer 13

Basal Lamina

Question 14

Transmembrane

Answer 14

Hemidesmosomes

Question 15

Four classes of collagen structure

Answer 15

Fibrils joined together by other extracellular matrix proteins…including fibril-associated collagens (Facit).
Transmembrane and Network-forming

Question 16

Four classes of collagen structure

Answer 16

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.

Question 17

The Collagen ‘Assembly Line’

Answer 17

Intracellular trafficking through the secretory pathway – exocytosis.

Fibril assembly begins in fibripositors, and is completed in the extracellular space.

Question 18

Medical importance of Collagen

Answer 18

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.

Question 19

Fibronectins Connect Cells to Collagenous Matrices

Answer 19

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.

Question 20

Continued

Answer 20

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.

Question 21

Fibronectins contain domains called Fibronectin repeats

Answer 21

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

Question 22

Formation of fibronectin fibres requires contact with the cell surface

Question 23

Elastin Fibres Impart Flexibility to Tissues

Answer 23

Elastin is organised into elastic fibers:

Core region enriched in elastin proteins.

Hydrophobic and Hydrophilic regions.

Tough coating called microfibrillar sheath

Question 24

Elastin Fibres permit tissue flexibility

Answer 24

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.

Question 25

Ratios

Answer 25

The ratio of collagen : elastin secreted by cells determines the elasticity of the ECM and therefore the tissue.
Blood vessels, skin and lungs have high levels of elastin – flexibility is important here.

Question 26

Ageing

Answer 26

The important role of collagens and elastins is demonstrated during the process of ageing.

Over time collagens become increasingly cross-linked and inflexible.

Also elastins are lost from tissues like skin.

In elderly people bones and joints are less flexible and skin becomes wrinkled

Question 27

Proteoglycans provide hydration to tissues

Answer 27

The sugars are glycosaminoglycans (GAGs) bound to core proteins.
Proteoglycans ensure the ECM is a hydrated gel.
Negative charge attracts water

Question 28

Hyaluronan forms enormous complexes with proteoglycans

Answer 28

The aggrecan complexes bind to molecules and attract water. hyaluronan

Absorbs compressive forces and acts as a lubricant.

Important for cartilage.

Question 29

The Basal Lamina Is a Specialised ECM

Answer 29

Lies immediately beneath epithelial cells.

Basement membrane

Question 30

What does the BL contain

Answer 30

Contains ~20 different proteins including some only found only in this structure.

Contains:
- type IV collagen
- laminin
- Heparan Sulfate Proteoglycans and nidogen

Question 31

Functions of the BL

Answer 31

Serves as a structural support – hemidesmosomes.

Selective permeability barrier – regulates the movement of molecules and cells, and protects against infection.

Proteoglycans bind and concentrate proteins

Question 31

Laminin

Answer 31

Lamina lucida and lamina densa.

Laminin links the basal lamina to the collagen network.

Question 32

Properties of Laminin

Answer 32

Large protein – 850 kDa.
3 long polypeptide chains – α, β, γ.
Disulphide bonds hold chains together
Possesses binding sites for Type IV collagen.
Functions as a bridging molecule that attaches cells to basal lamina – inter-woven with collagen network.

Question 32

Laminins Provide an Adhesive Substrate for Cells

Answer 32

3 polypeptide subunits wrapped together to form a triple helical coiled-coil.

Each subunit extends “arms” out from the coil giving rise to a cross-shaped structure.

Question 32

wo types of junction adhere cells to the ECM via integrins:

Answer 32

Focal adhesions - connect the actin cytoskeleton to the ECM.

Hemidesmosomes – found only in basal lamina.

The basal lamina is a specialised form of ECM found at the basal surface of epithelial cells.

Question 32

Integrins Control a Vast Range of Cellular Functions

Answer 32

Consist of 2 subunits - α and β.

Principal surface proteins for holding tissues together.

Question 32

Hemidesmosomes

Answer 32

Junctional complex found at basal surface of plasma membrane of epithelial cells.

Contain α6β4 integrin and link to the Intermediate Filament network (not actin).