Editor’s note: Keratinization is an important aspect to skin health and appearance, which is why in recent years raw material developers have engineered ingredients to influence its underlying mechanisms. Following is an excerpt adapted from Physiology of the Skin, Third Edition, which explores the process of keratinization.
The process of keratinization in human skin is necessary to form a shell-like, non-living protective covering over the body. As keratinocytes migrate toward the outermost layer of the skin, i.e., the stratum corneum (SC), they go through many changes until finally the protein shell left behind can form the skin barrier. The total renewal process of migration from the basal cell layer to the SC takes about 28 days. To better understand this process, it is first important to review the entities involved.
Stratum corneum: Fibrous proteins and lipids make up the corneocytes of the stratum corneum. Each corneocyte develops as a single cell that is integrated into the stratum corneum. On the face and back of the hands, the stratum corneum is less than 20 microns thick. Figure 1 shows the dimensions of the stratum corneum, compared with other skin layers.
The formation of these corneocytes is a complex process and each step requires one or more enzymes. Although many of the details are known, the complete process is not; thus the details have been reduced to present as clear a picture as possible of the formation of a simple corneocyte.
Basal cells: Basal cells form the bottom or innermost layer of the epidermis. These cells are anchored to fibers in the dermis called the lamina densa by means of structures called hemidesmosomes, from the Greek words desmos meaning “a band”; soma meaning “body”; and hemi meaning “half.” Hemidesmosomes consist of a dense plaque on the plasma membrane that contains integrin molecules that pass into the lamina densa and attach to fibronectin fibers. Within the cell, the integrin molecules are attached to cytoskelatal intermediate filaments.
Integrins are specialized extracellular matrix receptors in the cell membrane. These glycoproteins bind to extracellular adhesive proteins such as fibronectin in the dermis (see Figure 2). Intermediate filaments are intercellular proteins that bind to the fibrous components of the cell and cytoskeleton, and bind to the hemidesmosome plaque. Finally, laminin is an adhesive protein that attaches the cell surface to the basal lamina, often through integrins.
Steps in Skin Renewal
Step 1, Forming the spiny layer: In the process of skin renewal, first the basal cell must break the attachment to the dermis, round up, undergo mitotic division of the nucleus, and split into two new cells. While the mother cell is able to divide many times, the daughter cell is programmed to become a corneocyte and die—i.e., it cannot receive or send messages to lower cells in the epidermis. After being formed, the daughter cell is anchored to the basal cell by a structure similar to the hemidesmosome, known as a desmosome since it connects to two cells via fine, whisker-like projections into the cells.
Step 2, Differentiation into a corneocyte: The daughter cell then splits off from the basal cell and becomes a partially differentiated cell that cannot revert to a basal cell. A major change has occurred in the nucleus of the daughter, which has been programmed to become a corneocyte. The basal cell pushes the daughter cell up into the epidermis to form the second layer of the skin known as the stratum spinosum or spiny layer.
These spines are actual projections of fibrous proteins in the desomosomes—the structures that connect the cells of the epidermis. The spiny cells are hooked together by desmosomes at the top, sides and bottom that connect them not only to the basal cells, but also to adjacent cells; as noted, desmosomes like a hemidesmosomes except they join cells to other cells rather than to the lamina densa or basement membrane.
A complete set of organelles, such as nucleus, Gogli apparatus and mitochondria, remains in the spiny cell, though each is beginning to undergo changes. Membrane-coating granules and lamellar bodies are beginning to form and can be seen in the cytoplasm. A great deal of enzyme activity is creating lipids and proteins, while other enzymes are beginning to take apart the interior of the cell in preparation for the next step.
Step 3, The granular layer: The granular layer, also known as the stratum granulosum, is the layer in which marked changes to the kerantinocytes occur rapidly. Specifically, the cells are flattened, though still viable, and lamellar bodies are observed in the upper portion of the cytoplasm in the cells. These lamellar bodies contain stacks of flattened lipid vesicles. As the cell is slowly taken apart and new structures form, dramatic changes occur.
Step 4, The stratum lucidum: An abrupt transition of the granular cells to the stratum lucidum layer ends in the final stages of differentiation and leads to the cornification of the cells. The stratum lucidum is often difficult to see with the light microscope, as the cells are further flattened and quite thin. Proteases and nucleases destroy the cellular organelles, leaving only the keratin filaments in the intracellular matrix that are composed of broken down keratohyalin granules.
The membrane-coating granules fuse with the cell membrane and release their contents into the intercellular spaces, forming intercellular lipids that are organized into a multilamellar domain. These lipids include cholesterol, ceramides and fatty acids. The final stage is the addition of a protein envelope, called involucrin, to the cell membrane, which forms the cornified cell and gives it greater strength.
Step 5, Corneocyte formation: Finally, the last stage is the formation of the corneocyte. As noted, the outer envelope is composed of the protein involucrin, and it is under this envelope that a lipid envelope called the corneocyte lipid envelope is formed; beneath this layer are the keratin matrix proteins (see Figure 3).
Keratinization is an important aspect to skin health and appearance. To better understand this process, read Physiology of the Skin, Third Edition.
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