29. Extracellular matrix

You should know that adhesion means to glue or bind something together, so adhesion molecules are molecules that bind cells to other cells or to the ECM.

Binding cells to each other

Cells bind to each other by producing long proteins that attach to the cytoskeleton inside the cell and to similar long protein attached to other cells. This type of protein is called cadherin (you can think of them as cell adherins). They’re found in cells that are in the tissues, outside of the blood. One cell produces a cadherin molecule that attaches to a cadherin molecule produced by another cell that it should attach to. Cadherins are important in cell migration, and in making organized tissues out of individual cells. Ca2+ is needed for cadherin binding (the c in cadherin actually stands for “calcium-dependent”, not “cell”).

Another type of adhesion molecule are the selectins. They’re found in cells that live in the blood. There are three types of selectins. E-selectins are found on Endothelial cells, L-selectins are found on Lymphocytes and P-selectins are found on Platelets and endothelial cells.

In the synaptic cleft (the synapse between two neurons), many adhesion molecules can be found, like neurexin, neuroligin, cadherin and Ig-superfamily members. The first two are mutated in the case of autism.

Binding cells to ECM

The adhesion molecules that bind cells to the ECM are called integrins. They also require Ca2+ to bind.

The basal lamina

The basal lamina is a thin sheet that lies under all epithelium and works as an interface between the epithelium and connective tissue. It’s composed of laminin, type IV collagen, nidogen, perlecan, glycosaminoglycans and integrins.

The extracellular matrix

The ECM is an extracellular skeleton that provides support and strength for cells, but also has a role in regulation. It’s comprised of both fibrous and soluble proteins, and fibronectin, laminin, proteoglycans and glycosaminoglycans. The ECM is produced by fibroblasts.

There are several important glycosaminoglycans we should know. Hyaluronate can be found in the synovial fluid and vitreous humor in the eye. Chondroitin can be found in the skin, hair and bones. Keratan is found in skin. Heparin is mostly known as an anticoagulant, but it’s also found in ECM.

Collagen

Many types of collagen exist, but type I, II and III are the most common types. Collagen molecules are post-translationally modified by hydroxylation, sulfation and glycosylation. We should know the details of 3 types:

Type I collagen is found in scar tissue. Type IV is found in all basal lamina. Type XI is found in cartilage.

Because vitamin C is needed for the enzyme proline hydroxylase, which hydroxylases proline residues in collagen molecules, a deficiency of this vitamin will cause problems with the collagen. This disease is called scurvy.

Elastic fibers

Elastic fibers have two important components. The main component is elastin, which is rich in hydrophobic amino acids like proline and glycine. The other important component is microfibrils. The main component of microfibrils is fibrillin. Mutation in the gene for fibrillin causes Marfan’s syndrome.

Collagen and elastic fibers have multiple differences:

Property	Collagen	Elastin
Has hydroxylated lysine	Yes	No
Number of genes	Many	One
Structure	Triple helix glycine every third amino acid	Random coils
Glycosylated	Yes	No