Extracellular Matrix

Question 1

3 classes of ECM molecules

Answer 1

1. glycosaminoglycans (GAGs)
2. fibrous proteins (collagens)
3. non-collagen glycoprotiens

Question 2

What is the ECM

Answer 2

Extracellular matrix surrounding cells - ‘mesh’ of carbohydrate chains and proteins that performs a wide range of functions
Complex and intricate network of macromolecules made of different proteins/polysaccharides that are locally secreted and assembled into an organised meshwork

Question 3

Glycosaminoglycans

Answer 3

Highly negatively charged unbranched polysaccharide chains composed of repeating disaccharide units covalently linked to proteins as proteoglycans.
They can’t fold up and attract positive ions so swell with water and form gels that can absorb compression forces because of turgor and high osmotic pressure (eg. knee cartilage)
They occupy a large volume relative to their mass because of their stiff chains and hydrophilic nature

Question 4

Fibrous Proteins, ie. Collagen

Answer 4

Typical collagen structure with long stiff triple alpha helical chains organised with H-bonding.
Resists stretching/tensile forces and can assemble into fibrils
Humans have 42+ types of collagen

Question 5

Non Collagen Glycoproteins

Answer 5

‘Classical’ laminin - asparagine linked oligosacchrides
3 chains (with isoforms) linked by disulfide bonds
Self-assemble by side arm linking into mesh within the basal plasma membrane
Often found within the basement membrane or basal lamina

Question 6

Elastin

Answer 6

An example of a fibrous protein - are important for stretch and recoil of the matrix
Associate to form elastin
Composed of hydrophobic segments alternating with alanine/lysine rich segments
The non polar side chains allow stretching while the cross linking with other molecules encourages recoil into the original shape.
Woven with collagen fibers to limit their stretch
Loose random coil structure

Question 7

Basal Lamina

Answer 7

Specific specialised type of the ECM found in epithelial cells
It is thin, tough, and flexible
Functions: supports, attaches, separates, polarises, divides, differentiates, etc
Structure: laminin + nidogen + type IV collagen + perlecan

Question 8

Relevant Research into the ECM

Answer 8

Peterson et al 2009

• Used extracellular matrix as a scaffold to regenerate a rat’s lungs that actually functioned for a short period of time
• demonstrates a clinical application of the ECM to be used as a scaffold for organ or tissue regeneration, potentially with the patient’s own cells to prevent immunorejection

Question 9

Collagen Types

Answer 9

Type 1 = most common type that assembles into collagen fibrils
Type IX/XII = link collagen fibrils to each other and to the ECM
Type IV = network forming collagen that makes basal lamina
Type VII = form dimers that form anchoring fibrils that attach the basal lamina to connective tissue

Question 10

Cell Matrix Junctions

Answer 10

Matrix receptors (transmembrane cell adhesion proteins) help the matrix to influence cell activity, the key one being integrins.
Integrins transmit molecular and mechanical signals and can transmit one into the other based on the tension forces (mechanotransduction)
Switch between an active and inactive state, in which the inactive state is orientated in a way that means they can't interact with proteins. 
Many cells have anchorage dependence on the ECM and the integrins mediate this