Disulfide Bridges in Hair Shaft and Nail Plate, Examined More Closely

Hard and Soft Keratins Side by Side

Keratins belong to the intermediate filaments. One acidic type I keratin and one basic type II keratin pair up, their long central segments winding around each other. Many such pairs assemble into filaments roughly ten nanometers across.

In hair and nails, these filaments are embedded in a matrix of keratin-associated proteins. Some families of these companion proteins consist to an unusually large extent of cysteine, and so provide the anchor points for cross-links.

Names follow the 2006 international keratin nomenclature; quantities differ depending on the analytical method.

What a Disulfide Bridge Is, Chemically Speaking

The side chain of cysteine ends in a thiol group, meaning a sulfur atom bonded to a hydrogen. When two such groups meet and together give up two electrons and two protons, the sulfur atoms bond directly. The resulting double molecule is called cystine. This bond is considerably more stable than the hydrogen bonds that otherwise hold proteins in shape, and it can only be opened again with reducing chemicals.

The Follicle Works in Stages

A hair follicle does not produce without interruption. It alternates between an active phase, a short regression and a resting period, after which a new shaft is laid down. Each follicle keeps its own rhythm, so neighboring hairs are in different stages at any given time.

Cuticle, Cortex and Medulla

The cuticle consists of six to ten layers of flat cells that lie over one another like shingles, their free edges pointing toward the tip of the hair. The cortex beneath is made up of elongated, spindle-shaped cells in which macrofibrils of keratin filaments run in parallel. In fine hairs, the medulla is often missing altogether.

Hardening in the Keratogenous Zone

Above the bulb, the cortex cells manufacture their filaments and companion proteins, then break down their nucleus and organelles and give off water. The disulfide bridges form in parallel. In the cuticle and the inner root sheath, a further type of cross-linking is added: there, transglutaminases join proteins through so-called isopeptide bonds.

Layer Upon Layer Into a Nail Plate

The nail plate of a finger is usually only about half a millimeter thick. It is formed almost entirely by the matrix, which lies under the fold of skin at the base of the nail, and from there it slides forward over the nail bed.

• The rear portion of the matrix supplies the top layer of the plate.
• The front portion, visible on some fingers as a pale half-moon, forms the middle layer, which is also the bulkiest.
• Whether the nail bed adds a thin bottom layer as well is judged differently in the specialist literature.

Onychocytes Give Up Nucleus and Water

As they leave the matrix, the cells flatten, lose their nucleus and interlock with their neighbors through folds in their membranes. Unlike in the skin, they do not flake off but stay permanently joined. According to measurements, the water content of a healthy nail plate lies roughly between ten and twenty percent and shifts with air humidity.

The figures vary considerably between individuals and across age groups.

Selenocysteine and the Sulfur Chemistry of Horn Cells

Selenocysteine is inserted during protein synthesis by a dedicated mechanism and is therefore counted as the twenty-first proteinogenic amino acid. In the human genome, 25 genes are known for proteins containing this building block. The selenium atom gives up electrons more readily than sulfur does, which is why many selenoproteins convert thiol and disulfide groups in other molecules.

Thioredoxin Reductases in Keratinizing Epithelium

Thioredoxin reductases keep the small protein thioredoxin in its reduced form. Thioredoxin, in turn, can open disulfide bridges in other proteins. In a tissue where disulfide bridges are first held back and later formed on purpose, a system like this is of interest. In laboratory animals whose keratinocytes could no longer incorporate selenocysteine, skin and hair follicles developed conspicuous changes (Sengupta et al., PLoS ONE, 2010). Findings in genetically modified animals show what a protein is needed for; they say nothing about human nutrition.

For selenium, the EU has authorized two independent wordings.

“Selenium contributes to the maintenance of normal hair”

EU-authorized wording · Regulation (EU) No 432/2012

“Selenium contributes to the maintenance of normal nails”

EU-authorized wording · Regulation (EU) No 432/2012

With selenium, the gap between usual intake and the upper level is narrower than with many other trace elements.

Zinc, a Metal Ion With a Liking for Sulfur

Zinc does not change its charge in the body. It is therefore not needed for electron transfer, but as an ion that holds protein segments in a fixed arrangement or lines up water molecules and substrates in an active site. Its preferred partners are sulfur atoms from cysteine, nitrogen atoms from histidine and oxygen from aspartate or glutamate.

Metallothioneins and Zinc-Containing Enzymes in the Hair Bulb

Metallothioneins are roughly one-third cysteine and can bind up to seven zinc ions. In the skin and the follicle, they have been detected in the cell layers that renew themselves quickly. As long as a zinc ion sits on a thiol group, that sulfur is not available for a disulfide bridge; whether the follicle makes use of this is a subject of ongoing research. The papilla cells also show high activity of alkaline phosphatase, an enzyme with two zinc ions in its active site.

For zinc, the EU has authorized just one wording in this subject area. It refers to hair; for nails, zinc has no authorized claim.

“Zinc contributes to the maintenance of normal hair”

EU-authorized wording · Regulation (EU) No 432/2012

Out of the Letters We Received