Extracellular Matrix

Question 1

What is a simple way of describing ECM?

Answer 1

ECM is a complex network of proteins and carbohydrates deposited by cells most notably strands of collagen. It is made up of both fibrillar and non-fibrillar components. After being deposited, it becomes immobilised outside the cells and it fills in the spaces between cells.

Question 2

Give 3 key functions of ECM

Answer 2

1. Physical support (architectural)
2. Determine the mechanical and physicochemical (physical chemistry) properties of the tissue
3. Influence the growth, adhesion and differentiation status of the cells and tissue with which it interacts (instructional)

Question 3

What are the main 3 components of ECM in connective tissues?

Answer 3

1. Collagen
2. Multi adhesive glycoproteins e.g. fibrinogen
3. Proteoglycans

Question 4

Outline the structure of collagen

Answer 4

Each collagen molecule is made up of three α chains and can be a homotrimer or a heterotrimer.

The α chains form a triple helix.

In fibrillar collagens, each α chain is approximately 1000 amino acids long, forming a left-handed helix.

Every 3rd amino acid is glycine which is the only amino acid small enough to occupy the interior since its side chain is simply a hydrogen atom.

Crosslinking only occurs after the collagen has been secreted and provide tensile strength and stability.

Hydroxylation of proline and lysine to hydroxyproline and hydroxylysine increase stability through the formation of hydrogen bonds. Hydroxylation is the insertion of an oxygen into a c-h bond to form a c-o-h bond. Proline cannot form hydrogen bonds.

Not all collagens form fibrils. For example, type 4 collagen is present in all basement membranes and can associate laterally between triple helical segments as well as head to head and tail to tail between the globular domains to give dimers, tetramers and higher order complexes.

Question 5

What are basement membranes?

Answer 5

Flexible, thin mats of ECM underlying epithelial sheets and tubes.

These surround muscle, peripheral nerve and fat cells and underly most epithelia.

They are highly specialised ECMs containing a distinct repertoire of collagens, glycoproteins and proteoglycans.

In the kidney, they form a key part of the filtration unit as the glomerular basement membrane.

Question 6

Give 2 examples of diseases caused by anomalies in the basement membrane

Answer 6

Diabetic nephropathy – accumulation of ECM leading to thickened basement membrane restricting renal filtration.
Alport syndrome – mutations in collagen 4 result in a laminated and abnormally split GBM which leads to progressive loss of kidney function.