The Extracellular Matrix

Professor Alfred Cuschieri

Department of Anatomy, University of Malta

Objectives

By the end of this session student should be able to:

· Name the main extra cellular fibers and their locations

· Outline the molecular composition of collagen fibers

· Deduce the major consequences of defects in collagen formation on the functions of the extra cellular matrix

· List the factors that could affect collagen synthesis and affect wound healing

· Name the non-fibrillar components of extra cellular fibers and their functions

· Give examples of how cells interact with the extra cellular matrix

All cells are associated with extra cellular structures. The connective tissues consist predominantly of extra cellular structures, which consist of:

· Fibres - Collagen, elastic and fibrillin

· Matrix (amorphous ground substance)

· Fibroblasts and cells of various types

Collagen

Collagen is a family of extra cellular fibres that are widely represented in the body and have mainly mechanical functions. Collagen fibres provide strength and support.

10 types of collagen are known. They vary in :

a. molecular structure

b. morphology

c. distribution

Molecular Structure

All collagens have a basically similar molecular structure:

They contain large amounts of:

o Glycine (about 30%)

o Hydroxyproline and hydroxylysine (25%).

o (These amino acids are rare in other proteins)

o Oligosaccharide side chains (galactose and glucose)

Collagen is composed of molecules of pro-collagen. A pro-collagen molecule is composed of three polypeptide chains called a-chains, twisted in a helical fashion. The individual a-chains are termed pre-procollagen.

The general chemical structure of pro-collagen molecules is shown in the following diagram. (G – glycine; X – proline or hydroxyproline; Y – lysine or hydroxylysine; A – other amino acids)

– G – X – A – G – A – A – G – Y – A – G – A – A – G – X – A – G – A –

– A – G – X – A – G – A – A – G – Y – A – G – A – A – G – X – A – G –

– A – A – G – X – A – G – A – A – G – Y – A – G – A – A – G – X – A –

There are several different a-chains. They are found in different combinations in the different types of collagen, as shown below.

The following table illustrates the molecular structure, morphology and distribution of the first five types of collagen. The first five types are the most important ones. The other five are less important.

Collagen Type

Morphology

Molecular structure

Distribution

Type I

Fibres with periodicity of 63 nm.

a1-1; a1-1; a1-2

low in carbohydrates

· Ligaments

· Tendons

· Fasciae

· Bones

· Dermis of skin

· Sclera

Type II

Very thin fibrils forming a meshwork

a1-2; a1-2; a1-2

high in hydroxylysine and carbohydrates

· Hyaline cartilage

· Cornea

· Vitreous body

Type III

Loosely-packed network of thin fibrils

a1-3; a1-3; a1-3

low in hydroxylysine

· Associated with type 1

· Blood vessels

· Most internal organs

· Smooth muscle

· Foetal dermis

Type IV

Thin amorphous membrane

a1-4; a1-4; a1-4

Extensive hydroxylysine

Heavy glycosylation

· Basal laminae

Type V

Amorphous

a1-5; a2-5; a3-5;

high hydroxylysine;

low alanine

· Placenta

· Foetal membranes

· Skin

· Blood vessels

Biosynthesis of Collagen

This involves a series of sequential steps occurring in the rough endoplasmic reticulum and the Golgi complex:

1. Synthesis of a chains of pre-procollagen on ribosomes. A signal protein directs them to the RER .

2. Cleavage of signal protein forms procollagen

3. Hydroxylation of lysine and proline

Lysine à Hydroxylysine

Peptidyl lysine hydroxylase

Proline à Hydroxyroline

Peptidyl proline hydroxylase

Ascorbic acid is necessary to activate the hydroxylases.

4. Glycosylation: addition of galactose and glucose to some hydroxylysine residues. The enzymes galactosyl transferase and glycosyl transferase are required for this process.

5. Assembly of three a - chains to form procollagen. This involves the formation of disulphide bonds between parts of the polypeptide chains known as registration peptides, which occur at both ends of the pre-procollagen.