The Importance of Skin
It shouldn't be a surprise that the first thing we recognize when we look at someone is their skin. Even though we might believe that we have noticed someone's eyes or a friendly smile first, our brain has already developed a rudimentary assessment and assumption of that individual's racial group, health status, or hygiene based on skin type.
Skin: More Than Meets the Eye
The skin, however, has yet to be given the spotlight as, say, the brain, despite being the body's largest organ. We will quickly realize that this organ is more than skin deep, more than what meets the eye.
Beyond the Physical Barrier
Beyond the mere physical barrier skin provides, demarcating internal from external, skin boasts a host of functional properties necessary for our survival. These range from immune defense, heat regulation, moisture retention, and sensation detection to vitamin D synthesis.
The Integumentary System
The structures encompassed by skin anatomy, including hair, nails, sweat glands, and oil glands, each have unique functions, complementing the skin's overall function. This collective of functional subsystems and auxiliary structures is referred to by scientists as the Integumentary System. However, we will keep things simple in this blog and work with 'Skin' for now.
Skin Layers: Epidermis and Dermis
The skin consists of two layers: the outer layer, called the Epidermis, and the layer beneath it, called the Dermis. Below the dermis, there is a region that skin anatomists do not consider to be skin-like. This region is referred to as the hypodermis.
Epidermis
This is the visible layer where we apply skincare products. It's commonly referred to as skin, but there's more to it. The epidermis consists of 4-5 layers, arranged like a sandwich. Each layer has specific functions to protect and maintain water, determine skin color, and detect sensation. Anatomists have assigned these layers two-part Latin names, each beginning with "Stratum." From outer to inner, these are:
1. Stratum Corneum
2. Stratum Lucidum (only present in palms and soles)
3. Stratum Granulosum
4. Stratum Spinosum
5. Stratum Basale
Advancements in dermatology have called for further ascertainment of region-specific structures, functions, and biochemical processes. For instance, layers like the Stratum Corneum are further subdivided into a Stratum Compactum and Stratum Disjunctum (upper and lower corneum, respectively).
Dermis
The dermis sits just beneath and is stitched to the overlying epidermis by protein rivets called Hemidesmosomes, without which the epidermis would slough off after a routine shower. The interface of dermis and epidermis is referred to as the Dermal-Epidermal Junction. It can be seen under light microscopy as an undulating interdigitation of the dermis and epidermis (Dermal Papillae & Rete Ridges), necessary to withstand shear forces.
Layers of the Dermis
The dermis is further divided into two layers:
1. Papillary Layer – A highly vascularized, thin connective tissue meshwork of loosely packed Type I and Type III collagen.
2. Reticular Layer – A thick connective tissue layer of densely packed collagen.
Notable structures found in the dermis include:
-Blood vessels (absent in the epidermis)
-Sensory receptors (Pacinian corpuscles, Ruffini's corpuscles, Meissner's corpuscles, thermoreceptors, nociceptors)
- Sweat glands (apocrine, eccrine)
- Pilosebaceous units (hair follicle and sebaceous gland)
- Lymphatics
Also resident in this layer are unique structures called Dermal Fibroblasts, tiny cell factories that manufacture fibrous scaffolding that offers support, strength, and flexibility to the overlying epidermis. Fibroblasts are essential for the skin's plumpness. Skin becomes less supple, wrinkled, and prone to everyday insults as we age, due to the progressive decrease in fibroblast activity and reduced production of youthful compounds like elastin, collagen, hyaluronic acid, and chondroitin.
A Note on Aging
Chronological aging refers to the natural passage of time; biological aging is the body's internal wear and tear; photoaging results from skin damage due to prolonged sun exposure, accelerating aging signs like wrinkles and pigmentation. Anti-aging skincare products aim to reduce visible signs of aging, such as wrinkles, fine lines, and age spots. These products often contain ingredients like retinoids, antioxidants, and peptides that promote collagen production, improve skin texture, and enhance hydration, helping to maintain a youthful and radiant complexion.
Hypodermis/Subcutaneous Tissue
While not considered cutaneous or skin-like, the hypodermis, located underneath the skin proper (epidermis and dermis), plays some noteworthy roles. It mainly comprises fatty tissue and blood vessels, ensuring thermal insulation and temperature regulation. It also serves as a shock-absorbing cushion, protecting deeper organs against blunt trauma. Skin contouring and appearance are partially attributed to this layer's fat stores.
Fun Fact
Skin has a surface area of about 20 square feet, roughly the size of a picnic blanket.
The Journey of a Skin Cell
We will start by discussing the epidermal sublayers and their functions in the context of a skin cell's journey from the bottom (Stratum Basale) to the top (Stratum Corneum). As a guiding principle, a skin cell called a keratinocyte is programmed to transform into a deactivated, though not entirely dead, flattened skin cell known as a corneocyte.
The life cycle of a keratinocyte can be summarized in three stages:
1. Proliferation
In this stage, keratinocyte stem cells multiply to increase cell numbers.
2. Terminal Differentiation
Structural and physiological changes occur, transforming the keratinocyte into a corneocyte.
3. Desquamation
The final stage is the shedding of corneocytes, commonly called "dead skin."
This entire sequence of events, referred to as Epidermal Turnover, takes on average 28 days, or about 4 weeks.
Considerations in Skin Care
This important fact should be considered when testing skin care products to make a sound judgement on product performance efficacy. Since epidermal turnover takes about 28 days, product testing should span this period to assess true effectiveness.
Skin Conditions and the Keratinocyte Journey
Common skin conditions like Eczema, Psoriasis and Rosacea are often caused by external factors (e.g., UV damage, poorly formulated skin care products) or internal disruptions (e.g., genetic mutations) along the skin cell journey. Recognizing how these factors impact keratinocyte behavior can help in managing and treating these conditions effectively.
The Foundation of the Epidermis: Stratum Basale
The Stratum Basale is the lowest and thinnest of the epidermal layers, comprising a single row of tightly packed cuboidal to low columnar cells fastened to each other by protein buttons called Desmosomes. These desmosomes confer horizontal strength and rigidity to the layer, ensuring stability. Simultaneously, Hemidesmosomes resist shear forces by anchoring these cells to an underlying specialized extracellular matrix called the Basement Membrane.
The Basement Membrane: A Sturdy Foundation
The **Basement Membrane** serves as a sturdy platform for overlying epidermal layers to be sequentially stacked upon. It also acts as a barrier, compartmentalizing the **Dermis** from the **Epidermis**. Unlike the other epidermal layers, Stratum Basale exhibits high cellular activity when observed microscopically.
Cellular Proliferation in Stratum Basale
Keratinocytes in this region continuously clone themselves through **mitosis**, pushing older cells upward, creating space for new ones. This process is called **Cellular Proliferation**, making Stratum Basale also known as **Stratum Germinativum**, reflecting the germinative nature of keratinocytes in this layer.
The Foundational Players
Melanocytes
Stratum Basale is composed of three main cell types: Melanocytes, Keratinocytes, and Merkel Cells. Melanocytes account for about 5% of all epidermal cells and are responsible for producing the pigment Melanin. This pigment is synthesized inside specialized cell compartments called Melanosomes.
Melanocytes send tentacle-like projections between overlying keratinocytes, transferring melanin to them. This pigment plays a critical role in determining skin colour and provides moderate UV protection by forming a dome-shaped barrier over the nuclei of keratinocytes, known as the Melanin Barrier or Photoprotection Barrier.
Interestingly, the hues of skin colour depend on how much melanin is produced rather than the number of melanocytes present.
Keratinocytes
Keratinocytes make up around 85% of the total epidermal cell count, truly the stars of the skin’s cellular life cycle. Keratinocytes contribute significantly to the Skin’s Permeability Barrier, a critical aspect of skin's physical protection and waterproofing ability.
Merkel Cells
Named after German anatomist Friedrich Merkel, Merkel Cells are specialized mechanoreceptors that detect touch sensations, allowing us to be aware of physical contact with our skin. These cells account for about 6-10% of epidermal cell abundance and play an important role in sensory perception.
Fun Fact
The Fitzpatrick Scale of Skin Phototypes was established in 1975 by dermatologist Thomas B. Fitzpatrick as a model for determining sun sensitivity (tanning tendency) in relation to skin colour.
The Prickle-Cell Layer: Stratum Spinosum
The Stratum Spinosum, also known as the Prickle-Cell Layer, is the second layer above the Stratum Basale and the thickest of all the epidermal layers, consisting of 8-10 cell layers. This layer has been further divided into upper and lower regions due to the unique physiological and biochemical processes that take place within them. Its primary role is to set the stage for Terminal Differentiation (Cornification/Keratinization).
Moisture Retention and Skin Elasticity
A major preparatory step in this layer is moisture retention, which is crucial for the complex physiological mechanisms that drive terminal differentiation. A fishnet-like mesh made of the structural protein keratin ensures adequate moisture trapping, manifesting as supple skin with good elasticity. Keratin Intermediate Filaments form the cell's internal skeleton (cytoskeleton), offering strength and rigidity, much like the body's skeletal system. As the keratinocyte terminally differentiates, these intermediate filaments harden and bundle together to assist in the development of the skin's Permeability Barrier.
Immune Defense in Stratum Spinosum
The body's first line of immune defense is present in this layer as Langerhans Cells, which make up 5% of the epidermal cells. These tissue-resident macrophages act as sentinels, constantly sampling foreign particulates like microbes and allergens. They either digest these by receptor-mediated endocytosis or present them to other immune players, initiating a coordinated immune response. Dysregulated immune activity can lead to inflammatory issues, as seen in conditions like eczema and rosacea.
Biochemical Processes in the Upper Stratum Spinosum
At the Upper Stratum Spinosum, several biochemical processes take place, laying the groundwork for Terminal Differentiation—the transformation of keratinocytes into corneocytes. These processes involve two major structural modifications of the keratinocyte's plasma membrane:
1. Protein Modification: The development of a Cornified Cell Envelope.
2. Lipid Modification: The formation of a Multilamellar Lipid Structure.
At this stage, cellular machinery like free ribosomes and the Golgi apparatus begin manufacturing subcellular structures that kick off the cornification process. These structures include:
- Keratohyalin Granules: Found within the cytosol, these insoluble protein granules contain precursor proteins such as profilaggrin, tricohyalin, loricin, and keratin, which help in protein modification.
- Odland Bodies: Pouch-like repositories that eventually migrate to the Stratum Granulosum, where they are referred to as Lamellar Bodies. They contain precursor lipids (cholesterol sulfate, glucosyl ceramides, sphingolipids, and phospholipids) as well as lipid-assembly enzymes that assist in lipid modification of the keratinocyte membrane.
Odland/Lamellar Bodies also contain additional biochemical and immunological agents such as kallikrein, cathepsin, and beta 2 defensins.
Calcium Gradient and Enzymatic Activity
A key discovery in the Stratum Spinosum is the gradient of intracellular calcium (Ca2+) levels, with elevated Ca2+ concentrations in the Upper S. Spinosum compared to the lower region. This difference in calcium concentration triggers early enzymatic mechanisms of Cornified Cell Envelope development by activating Transglutaminase 1 (TGase 1) and crosslinking major structural proteins. These activities reach their peak in the Stratum Granulosum.
Stratum Granulosum: The Moisture Barrier
Stratum Granulosum, the thinnest layer of the epidermis (3-5 cell layers), lies just above the moisture-rich Stratum Basale and Stratum Spinosum, and below the moisture-poor Stratum Lucidum and Stratum Corneum. This layer appears granular under the microscope due to the abundance of keratohyalin granules in keratinocytes. The main role of this layer is to drive the modification of keratinocytes during the cornification process.
Keratin filaments within the keratinocytes begin to harden, flatten, and bundle together, a process that peaks in the Upper Stratum Granulosum. Intermediate-associated proteins like tricohyalin and filaggrin also become activated at this stage, contributing to water repellence and reducing Trans Epidermal Water Loss (TEWL). TEWL refers to the passive evaporation of moisture from the skin due to differences in water vapor pressure between the body and the atmosphere. If the skin fails in this role, significant water loss can occur, leading to severe dehydration or even death in extreme cases like third-degree burns. Even with intact skin, abnormal water loss can result in conditions like Xerosis, a group of dry skin disorders.
Cornification and the Cornified Cell Envelope
The cornification process continues in Stratum Granulosum as keratinocytes form their most crucial structure—the Cornified Cell Envelope. This structure results from both protein and lipid modifications. Protein modifications start by linking several structural proteins to build a scaffold-like support for lamellar lipids, which form a protective barrier against injury. The enzyme Transglutaminase 1 (TGase 1), activated by calcium gradients, crosslinks proteins such as loricrin, cystatin, filaggrin, and keratins to form a monomolecular layer of acylglucosylceramides beneath the plasma membrane.
Acylglucosylceramide, an omega-hydroxyceramide derivative, provides sturdy support for the deposition of multilamellar lipids on the keratinocyte surface. The lipid modification process begins once the lipid triad (ceramides, cholesterol, and free fatty acids) of Odland bodies have matured. These lipids are extruded from the Odland bodies through exocytosis and deposited on the plasma membrane, forming the multilamellar lipid structure essential for the skin's permeability barrier.
Lipid Structure and pH Gradient
Multilamellar lipids consist of approximately 40-50% ceramides, 25% cholesterol, and 10-15% free fatty acids, with the remainder being simple neutral lipids. The quantity and quality of ceramides are crucial for maintaining the multilamellar lipid structure, and ceramides can only be obtained nutritionally.
Another critical feature of Stratum Granulosum is the gradual decline in extracellular pH as you move upwards through the skin. This gradient decreases from a neutral pH of 7 at the lower layers to an acidic skin surface pH of 4.5 at the Stratum Corneum. This acidic mantle creates a hostile environment for harmful pathogens.
The Transitional Zone and Natural Moisturizing Factors
At the upper portion of Stratum Granulosum, known as the Transitional Zone, keratinocytes begin their final transformation into corneocytes. During this phase, several events occur simultaneously, completing the keratinization process. One notable event is the formation of Natural Moisturizing Factors (NMFs), which are high molecular weight compounds that help the skin retain moisture. These compounds, such as amino acids, pyrrolidone carboxylic acid (PCA), and lactate, are vital for skin hydration and reduce TEWL.
The Role of Caspase 14 and Filaggrin
The formation of these water-binding compounds is triggered by the enzyme Caspase 14, which, in the presence of elevated calcium levels and a low pH, degranulates keratohyalin granules, releasing dormant profilaggrin into the keratinocyte cytoplasm. Profilaggrin then converts to filaggrin, some of which breaks down into NMFs.
Filaggrin, along with other filament-associated proteins like trichohyalin, drives keratinization by aggregating keratin filaments (tonofilaments) into keratin bundles (tonofibrils). These tonofibrils harden the cell, strengthening the skin’s water barrier, formed in part by multilamellar lipids deposited on the plasma membrane and between cells.
Completion of Cornification: The Birth of the Corneocyte
As the keratinocyte loses its nucleus and cellular machinery, it becomes deactivated, though not entirely lifeless. Cornification is complete with the formation of the Cornified Cell Envelope and cellular deactivation, and the keratinocyte is now known as a corneocyte. At this stage, the region transitions from Stratum Granulosum to the outermost layer, the Stratum Corneum, where these specialized cells reside.
The Protective Layer of Thick Skin: Stratum Lucidum
Stratum Lucidum is a unique layer found only in palmoplantar skin—the skin of the palms of the hands and soles of the feet—where extra protection and durability are necessary. Anatomists refer to this type of skin as "thick skin," while the rest of the body is covered by "thin skin." Though Stratum Lucidum is typically about the same thickness as Stratum Granulosum (~3-5 cell layers), it serves a distinct purpose, enhancing the skin’s resilience in areas prone to friction and pressure.
A Rare Appearance in Thin Skin
Interestingly, some skin scientists believe that Stratum Lucidum can occasionally appear in "thin skin" under certain conditions, such as pruritic eczema. This variant of eczema is characterized by an intense urge to scratch, and it’s thought that the skin attempts to protect itself from the constant friction by forming a Stratum Lucidum-like layer. This may explain why those affected by conditions like atopic dermatitis often experience rough, leathery skin that requires hypoallergenic moisturizers and lotions to soften and soothe.
Keratinocytes in Stratum Lucidum
In this layer, keratinocytes are almost completely lifeless, tightly packed together to work with Stratum Granulosum in further enhancing the skin’s waterproofing abilities. This added protection is vital for the areas of the body that endure the most wear and tear, keeping them resilient and less prone to injury or damage.
The Final Frontier: Stratum Corneum
We’ve reached the last and outermost of the epidermal layers, Stratum Corneum. Like other layers of the epidermis, Stratum Corneum is divided into two regions: the Lower region, called Stratum Compactum, and the Upper region, known as Stratum Disjunctum.
Stratum Compactum: The Last Stage of Cornification
Stratum Compactum captures the final events of cornification, occurring in the Transitional Zone, as well as the process of *compaction*. Compaction involves stitching together specialized corneocytes (also known as squames). The tonofibrils, formed during keratinization, act as specialized protein rivets called corneodesmosomes, which stitch adjacent corneocytes together in a serrated pattern—a process known as Corneocyte Compaction. This step is vital for the skin’s barrier defenses, particularly in preventing pathogens, allergens, and other invaders from penetrating while minimizing Trans Epidermal Water Loss (TEWL).
If the compaction process is incomplete due to a faulty cornification process (often caused by filaggrin protein deficiency or Filaggrin Mutagenesis), the permeability barrier is compromised. This can lead to skin conditions where the barrier fails to protect effectively .
Stratum Disjunctum: Shedding the Old, Welcoming the New
In the upper region, Stratum Disjunctum, skin cells fulfill their protective role and prepare for replacement. Here, desquamation—the shedding of corneocytes—occurs. This process is initiated by an acidic pH environment and activated by proteolytic enzymes like cathepsin and kallikrein serine proteases (KLK5, KLK7, KLK14). The shedding process is intricately regulated to avoid excessive or insufficient shedding by balancing proteolytic enzymes with inhibitors such as Lymphoepithelial Kazal-Type Inhibitor (LEKTI) and Cholesterol Sulfate.
Maintaining this balance is essential to ensure proper thickness of the Stratum Corneum and the integrity of the skin's barrier defenses. As corneocytes move from the lower to upper layers, the rate of desquamation increases. Under light microscopy, this orderly process appears as a "honeycomb" pattern—the structural remnants of cornification .
Hydration and Skin Health
Hydration throughout the Stratum Corneum is key to facilitating this intricate process. In dehydrated skin, desquamation can become disordered, leading to a buildup of squames that can appear scaly and compromise the skin's protective barrier. Maintaining the delicate balance of desquamation is a hallmark of a healthy Stratum Corneum. Well-formulated skincare products are essential for maintaining hydration throughout the Stratum Corneum, with balanced blend of nourishing, biocompatible ingredients. Check out our epidermal Honey and Moringa infused organic skincare products, sustainably packaged for the elegant person.
The Marvel of the Stratum Corneum
The research of corneobiologists, dermatologists, and other skin scientists continues to shed light on the wonders of the Stratum Corneum and the entire integumentary system. These findings are paving the way for advancements in modern skincare formulations, making it possible to maintain a healthy, functioning skin barrier.
Continue the Skin Science Saga:
Skin Barrier Defense, where we dive deeper into how this essential system protects you every day from pollutants, UV and pathogens.
Samuel Jones
Bsc. Biological Sciences (Hons.)
PG. Dip. Organic Personal Care/Cosmetic Science
PG. Cert. Barrier Disordered Skin
PG. Cert. Beekeeping
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