The chemistry of our skin (revised for 2018)

I’ve updated this post with interesting things I’ve learned in the past two years. The original post can be found here

Your skin is composed of three layers – the epidermis, the dermis, and the hypodermis or subcutis. Our main focus will be the epidermis or the outer layer of our skin.

I find it interesting that the upper level of our skin does not contain any veins or arteries, and is nourished by a concept called diffusion, in which there is a movement of molecules from a region of higher concentration to a region of lower concentration. In the case of our skin, the living cells of the epidermis receive what it needs from the underlying dermal capillaries. It can also move nutrients from the outer layer inwards, which is how our creations work to moisturize our skin!

The epidermis consists of five layers or strata…
• the stratum basale (at the bottom)
• the stratum spinosum
• the stratum granulosum
• the stratum lucidum (also called the corneoepidermial junction)
• the stratum corneum (at the top) This is the layer that concerns us the most when making products.

Skin cells are formed through mitosis in the stratum basale (the bottom layer). Their shape and composition change as they move up to the stratum corneum. As they move up, they release cytoplasm and take on keratin. When they reach the top layer, they are sloughed off. (This process is called keratinization). This top layer of skin is responsible for creating the skin barrier – keeping water in and keeping the world out! There are somewhere between 10 to 30 layers of these dead cells on the top layer of your skin.

When the cells reach the stratum corneum, these corneocytes are considered dead cells as they contain no organelles inside. They are completely flattened and are now filled with keratin and lipids, fatty acids, and ceramides. Keratin is a protein that keeps our skin hydrated by preventing water loss or absorbing water from the atmosphere. It is responsible for the “spring back” or elasticity of our skin.


When your skin cells reach the top layer of the stratum corneum, they’ll sit there for about 14 days before sloughing off. This process is called desquamation or exfoliation. Scientists know there are enzymes that will break the bonds between the corneocytes, but there’s still so much to be learned about the entire process!

The corneocytes are linked in the lower levels of our stratum corneum by corneodesmosomes (which are macromolecular glycoprotein complexes or “proteins that hold corneocytes together”). As they move from the lower to outer region of the stratum corneum, they are degraded by enzymes, found in the intercellular spaces. The activity of these enzymes is affected by the content of the lipids found in the spaces and the water content of our skin.

Ideally our skin would have about 10% to 20% water content. When the amount falls below this, we see dry, flaky skin. The stratum corneum becomes thicker (called hyperkeratosis), and instead of detaching cell by cell, the corneoctyes detach in sheets or scales. This is why we see that white or grey flakiness on our skin!

The desquamation process varies with skin type and skin colour. Darker skin usually has a higher spontaneous desquamation rate than paler skin (up to 2.5 times faster), which can lead to increased levels of dry skin. We can speed up this process by using chemical or physical exfoliants.

NATURAL MOISTURIZING FACTOR (NMF) The lovely fluids inside the corneocyte is called our skin’s natural moisturizing factor (or NMF). When we attract water to our skin from the atmosphere or apply lotions containing water to our skin, the water dissolves these molecules and they act as humectants in our skin drawing water from the atmosphere. And the major components of this NMF is sodium lactate, urea, and pyrrolidone carboxylic acid (or sodium PCA), all great humectants.

Natural moisturizing factor (NMF) is found within the corneocytes, and makes up 20% to 30% of the dry weight of the stratum corneum. It consists of amino acids (40%), sodium PCA (12%), lactate (12%), urea (7%), ions (18.5%), sugars (like glycerol – 8.5%), and a few other things. These are water soluble humectants (meaning they draw water out of the atmosphere to our skin) that have a huge impact on the biochemical and mechanical properties of our skin. Having an adequate NMF level in our skin can prevent or reduce skin tightness, cracking, scaling, and flaking. It improves our skin’s plasticity (thanks to the interactions of the amino acids with keratin) and helps maintain skin’s barrier properties.

Most of the amino acid based parts of the NMF are derived from the enzymatic hydrolysis of proteins, filaggrin, and the corneodesmsomes of our skin. (This is actually a process called proteolysis – (Wiki) Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.)

Filaggrin is a really important protein found in our skin! The degradation of this protein makes it possible for our outer skin layers to maintain an adequate water supply in dry or arid environments. When our skin is occluded or humidity is high, there is a minimal breakdown of this protein. When we are in more arid climates, the filaggrin breakdown increases to produce more NMF. More NMF is a good thing!

The contents of the NMF do more than act as humectants. The lactate and potassium can affect the pH and stiffness of the stratum corneum. The lactic acid stimulates ceramide biosynthesis and improves barrier function. The hyaluronic acid maintains hydration and structural integrity of our skin. It also interacts with intercellular lipids and regulates the mechanical properties of the stratum corneum.

Finally, we come to glycerol (also known as glycerin, one of the sugars found in our skin). It’s derived from the breakdown of the triglycerides found in our sebum. It acts as a really awesome humectant in our skin and works well when applied to our skin. Study after study has shown that adding glycerin to our products can only help our skin maintain or increase hydration and enhances our skin’s pliability.

Aquaglyceroporins are “membrane proteins that form water channels over cell membranes. They faciliate transport of water and solutes like glycerol or urea.” (This document, p. 78) In other words, aquaporins regulate the water flux in our skin (specifically in our epidermis, or outer layer of our skin). They are embedded in our cell membranes to help with the transport of water. The one that interests us is listed as aquaglyceroporin-3, or AQP3 for short.

We don’t find AQP3 in our stratum corneum or first layer of our skin – it’s found in the basal layer (lowest level in the picture) to just below the stratum corneum. “In the viable epidermis, AQP3 provides a short circuit for water between the base of the epidermis and the SC in order to maintain constant water content in viable epidermis. In addition to its water permeability function, AQP3 is also permeable to solutes such as urea and glycerol, and studies have suggested its role in the transport of these solutes within the epidermis.” (Page 78, this document).

Why do we care about AQP3? Because it’s interesting, and because it could be the reason you’re suffering from dry skin that doesn’t seem to get better no matter how much lotion you apply.  “AQP3 is expressed in the basal layer of mammalian skin and is responsible for the epidermal water/glycerol transport. The hydration of SC [stratum corneum], evaluated by high-frequency skin surface conductometry and the estimation of radioactive  3H2O, was reduced in AQP3-deficient mice.” (Page 25, this document). What can you do about this dry skin? “Although AQP3 acts as a water channel in the basal keratinocytes, the reduced SC hydration could not be corrected by skin occlusion or exposure to a highly humid environment.” (page 25, same document).


The water levels of the epidermis are high – about 70% – but these levels drop sharply at the junction of the stratum granulosum and stratum corneum from this high of 60% to about 15% to 30%. It is believed this is where the barrier of water loss is located, in the corneoepidermal junction. “It is widely accepted that the barrier function to paracellular influx or loss of water and solutes is primarily provided by intercellular lipids filling the space between cells of the uppermost living cell layer and the SC. However, recent studies suggest that tight junction structures exist in the human epidermis and are also required for the control of skin permeability.

Tight junctions (TJ) are intercellular structures that control paracellular permeability (i.e., the diffusion of water and solutes across intercellular spaces). They consist of transmembrane proteins (e.g., claudins, occludin, and junctional adhesion molecules) and of plaque proteins (e.g., zonula occludens proteins ZO-1, ZO-2, and ZO-3; Fig. 3).50 Studies in animal models have suggested the importance of TJ for control of skin permeability. Furuse et al. reported that mice lacking claudin-1 die because of significant body dehydration.” (Page 79, this document).

In other words, although we’ve long thought that the barrier to water loss was thanks to the intercellular lipids, like our natural moisturizing factors and stratum corneum lipids, it turns out that there’s another structure – the tight junction – that can help prevent moisture loss.

Prevention of water loss is an essential part of why we make our products! Learn more by reading this post on transepidermal water loss


The stratum corneum is sometimes called the “horny layer” (did I hear a giggle there?) because the corneocytes are hornified with an outer layer of proteins to keep them solid. Many discussions about the stratum corneum likens the cell configuration to a brick wall, with the corneocytes acting as bricks and the lipid barrier structure as the mortar.

If you look at the picture to the left, you can see the individual cells of the stratum corneum. Think of those as bricks and the spaces around them filled with the lipid barrier structure to create a space-less layer.>The lipidic barrier structure consists of various fatty acids and their salts that have low solubility in water but are capable of forming a very stable layer. Their job is to keep irritants out and prevent trans-epidermal water loss. (That diffusion I mentioned before…that’s how we lose water!)

The thickness of the stratum corneum varies on your body. It is thinner, and therefore more permeable, on your face, forehead, and scrotum (if you have one!), and less permeable on your torso, arms, legs, hands, and feet. Your palms are particularly impermeable to most things, except water.

The water soluble natural moisturizing factor is found inside the corneocytes; the lipid soluble stratum corneum lipids are found outside the corneocytes.

They make up about 15% of the dry weight of the stratum corneum, and contain about 40% to 50% ceramides, 20% to 25% cholesterol, 15% to 25% fatty acids (those with C16 to C30 chain lengths, with C24 to C28 being the most common), and 5% to 10% cholesterol sulfate.

The lipids are arranged in a highly organized lamellar arrangement (fine layers alternating between different materials) with small amounts of water present. This is considered to be a very effective barrier to trans-epidermal water loss (TEWL). Water trying to escape the through the stratum corneum would have to navigate a complicated maze through the bilayer and the corneocytes to get to the surface of your skin – so the lipids and corneocytes make this a much harder task!

The ceramides in our skin are a major component of the structural organization of the lamellar bilayers. There are nine different types, each offering something to the organization of our stratum corneum and cohesion of the skin barrier.

There’s a subclass of ceramides called acylceramides, which are ester linked to hydroxy fatty acids, specifically linoleic acid – hence the concept that an oil high in linoleic or gamma-linoleic acid can help improve our skin’s barrier properties. In the winter, the ratio of the EOS-oleate increases which means the EOS-linoleate decreases; this happens with dry skin as well. This has a dramatic effect on lipid organization. (The EOS means it is linked to sphingosine.)

We need to treat the stratum corneum lipids well because without them, we end up with really dry, perturbed skin. Particular solvents (hexane, toluene) can damage the lipids and leave our skin defenceless. Harsh cleansers can also mess up the lamellar structure, leading to serious changes in the health of our skin.

Trans-epidermal water loss (or TEWL) is defined as a measurement of the quantity of water that passes from inside a body through the epidermal layer to the surrounding atmosphere via diffusion and evaporation processes. This is a continuous process over which we have little control. It can increase due to disruption to the skin barrier (wounds, scratches, burns, exposure to solvents or surfactants, extreme dryness) and is affected by humidity, temperature, season, and moisture content of the skin (hydration level). It’s been estimated we lose 300 to 400 ml/day.

TEWL is measured by a gadget called the ServoMed Evaporimeter (no, you can’t have one, it’s very expensive!) We lose the greatest amount of water through our palms, soles of our feet, backs of our hands, and forehead. The mechanisms of TEWL are not well known, but there are been many studies on it for differences in sex, race, and age. Interestingly enough, these studies have been inconclusive. The only real determinants of TEWL are damaged to skin, skin hydration, and atmospheric effects.

When the climate is dry, TEWL increases. When we have too little water in our skin – we want 10% to 20% or so – TEWL increases. When there’s damage to our skin – sunburn, burns in general, wounds – TEWL increases. In short, anything that assaults or insults our skin increases TEWL.

I love the idea of insulting the skin. This is one of those phrases that comes up a lot in my cosmetic chemistry textbooks, as well as the word “perturbs”. It seems to imply that our skin is really and truly alive with a personality that is easily offended. I wonder how many of my facial skin problems are the result of me yelling into the mirror “You are not as blemish free as I would like!” or “Why are you so sensitive?”

So what can we do to reduce TEWL? We can stay away from things that damage our skin, like too much sun or wind exposure, extremes in temperatures, or really scratchy sweaters. We can live in a humid climate or have a humidifier in the house (40% to 60% humidity is ideal). And we can make lovely creations that will trap water into our skin or add more when needed.


Our skin has an acid mantle, which is a fine, slightly acidic film on the skin that acts as a barrier to bacteria, viruses, and other icky things that might penetrate our skin. This acid mantle is a result of production of amino acids and lactic acid that settles on our skin. It is a good environment for the good bacteria and other tiny creatures that live on our skin, and they can protect us from chemical and natural attack by other tiny creatures or skin unfriendly chemicals.

We don’t want to mess with the acid mantle, so we need to formulate our products within the skin’s pH range – usually 5 to 8 is good. We don’t want to use harsh surfactants or very alkaline soaps as they can destroy the acid mantle, which leads to dry skin, reduction in the stratum corneum lipids, and lowered resistance to microbial or chemical assaults.


This is epidermal ground substance called glycosaminoglycans or GAGs, which bind water in the skin, resulting in increased hydration of skin and moisture retention. We need some of this stuff for normal collagen structure and functioning, but too much can lead to wrinkling in photo-damaged skin. Hyaluronic acid is a glycosaminoglycan. (Shar pei dogs have too much GAGs, hence their adorable wrinkled look.)


An increase in collagen production is a mighty fine thing indeed. As we age, we lose about 1% of our collage per year, which leads to reduced elasticity of our skin. With the reduction in the GAGs in our skin, we will appear less wrinkled

Collagen accounts for 18% to 30% volume of the dermis, and is rich in amino acids such as hydroxyproline, hydroxylysine, and glycine. It makes up the framework for so much of our body, and for our skin.

Elastin is found in our tissues and connective tissues. It helps our skin to spring back or resume its shape when it’s poked or moved.

So here’s the ideal cycle for our skin…Cells form in the lower layers and migrate to the upper layers. They contain NMF, which is now coated in proteins to make it more solid. A lipid barrier structure surrounds the corneocytes to keep our skin healthy. This all works to keep horrible things out and good things in – yay, skin!

If you really want to get into learning more about our skin, please read this document Skin hydration: A review of its molecule mechanisms. It’s simply fascinating and really in-depth. And I suggest that you read the posts below for more information. It seems silly for me to re-post them all when there’s not a ton of new information to add!

Harry’s Cosmetology

Epidermal barrier disorders and corneodesmosome defects

Corneodesmosin: Structure, Function and Involvement in Pathophysiology

Scratching the Surface

Cell death by cornification