Life
As a Skin Cell
Diana L. Howard Ph.D.
The International Dermal Institute
Published in Les Nouvelles Esthetiques November 2003
Today is my birthday. I have the distinguished pleasure of being a newly “born” keratinocyte which makes me the most common type of cell in the skin’s epidermis; as a matter of fact, we make up from 90 to 95% of all epidermal cells. Having just been through the cell birth process I am residing near the lowest layer of the epidermis which is called the basal cell layer; for those that may prefer a more formal name, my current residence is also called the stratum germinativum. While this location has its benefits, such as an abundance of oxygen and nourishment provided by the underlying local capillary system, my plans will not allow me to linger here long. You see, as a newly formed keratinocyte I am about to embark on a journey that will coincide with a cellular metamorphosis that will end when I reach my final destination, the stratum corneum. During my journey my structure and chemical make-up will continually change as I undergo a process called keratinization. Several major changes will occur as I go through this genetically programmed process of differentiation. I will lose the ability to reproduce, I will increase in size while my shape will flatten, new organelles will form together while some of my existing organelles will undergo a reorganization; eventually all of my organelles will be lost. In addition I will start to synthesize new proteins and lipids while my membrane properties will change. And finally, by the time I reach my destination I will be severely dehydrated having lost 70% of my water content. At the end of my journey I will be a dead corneocyte. But please do not confuse this with being non-functional. As a completely differentiated corneocyte I may be dead, but I am fully functional, particularly in terms of my ability to form a barrier and protect my sibling cells that lie beneath me. The itinerary for my journey is extremely well defined and is just part of my job as an epidermal cell. It will take me at least 14 days to reach my end point, the stratum corneum, and another 14 days until I transit through the stratum corneum and eventually slough off your body. So while the journey is scheduled to be about 28 days, it can vary depending on your age and the condition of the skin. Before I get ahead of myself, let me describe to you life as a newly formed keratinocyte.
As a new basal cell inhabitant my neighbors are actively dividing parent cells that coexist with a few immigrant cells known as melanocytes-more about them later. My parent cell is a stem cell that is responsible for maintaining the epidermis by continually renewing the cell population. It divided and gave rise to a daughter cell-that’s me. While I am destined to differentiate and mature, my parent cell will continue dividing forming additional daughter cell siblings.
Most of us basal cell residents are taller than we are wide and we all contain bundles of keratin filaments which form a type of flexible skeleton that helps us maintain our form. Fortunately, this keratin cytoskeleton still allows for flexibility which lets us to move out of the basal layer to migrate superficially while we undergo the keratinization process. As long as we reside in the basal layer we will be able to maintain open lines of communication with the underlying basal cell membrane at the dermal-epidermal junction. This unique association helps us maintain the structural integrity of the epidermis while allowing for regulation of keratinocyte proliferation, movement and differentiation.
I mentioned earlier that as a basal cell keratinocyte we coexist with melanocyte cells. These cells produce melanin pigment in jellybean-like capsules known as melanosomes. Melanocytes, are octopus-shaped cells with multiple dendritic arms, that facilitate transfer of melanosomes into neighboring keratinocyte cells. That’s what gives you and me our color. Regardless of skin color, the number of melanocytes found in the human body is fairly consistent. There is approximately one melanocyte for every thirty-six of us keratinocytes found in the epidermis. The amount of melanin, the type of melanin produced (whether it is eumelanin, a brownish-black pigment or phaeomelanin, a yellowish-red pigment), the size of the melanosomes and the distribution of melanosomes in the epidermis all contribute to the skin’s color and intensity—light vs. dark. In black skin, we not only see larger melanosomes with more melanin present, but more of them. They are seen as larger, individual, jelly bean-like structures surrounded by a membrane, where as melanosomes in Caucasian, Asian and Hispanic skin, are smaller, vary in size and shape, with many melanosomes clustered in a single membrane jacket.
Interestingly, melanosome transfer to keratinocyte cells like me, is stimulated by ultraviolet radiation, as well as hormones, which accounts for pigment formation from sun exposure and hormonal influence. When skin is exposed to sunlight the melanosomes reorient themselves around the exposed edge of our cell nucleus to protect it from UV irradiation. Once the keratinocyte begins its journey through the layers of the epidermis, enzymes degrade the melanin reducing the amount of pigment present in the outer most layers. Enough on melanocytes-lets get back to my story.
Once I migrate north, out of the basal cell layer I begin to change into a stratum spinosum cell. It’s here where the nature of my keratin proteins change somewhat. Sometimes they refer to me as a prickle cell. Regardless of what you call me, a prickle cell or a spiney cell, both names are derived from our
spine-like protrusions that occur when scientists look at us under the microscope. These spiney structures are actually an artifact that occurs as a result of shrinkage during the tissue processing and in real life they don’t really exist! However, the spines occur where there are desmosomes, or adhesion points between cells. Desmosomes are complex structures made of adhesion molecules and proteins, some of which require calcium ions in order to function. Once I reach this point in the epidermis my shape begins to change- I am more polyhedral in shape when residing in the lower spinosum levels and I take on a more flattened appearance a few layers out.
Another type of immigrant cell coexists with me in the spinosum layer. They are called Langerhans cells; these macrophage cells are present in all layers but are predominantly found in the spinosum layer. They have several identifying marks associated with them which makes them easy to distinguish from us keratinocytes. They have a pale cytoplasm, a convoluted nucleus, no obvious tonofilaments, and they lack the visible spines at the periphery of the cell. Langerhans cells, are part of the skin’s immune response system, and act as our first line of defense for the skin.
Now that I am a full- fledged spinosum cell you can also see characteristically large bundles of keratin filaments called tonofilaments that are organized around my cell nucleus; these extend out to the desmosomes on the outer membrane of my cell. It is thought that the filaments play an important role in helping me maintain cell cohesion with my neighboring cells and resisting the effects of abrasion, especially at the sites of the desmosomes. In areas that are subjected to continuous friction and pressure such as the soles of the feet, there are more of us that form a thicker stratum spinosum layer; in theory more cells, with more abundant filaments and desmosomes help protect the integrity of the epidermis in high friction areas.
When I reach the outermost layer of the stratum spinosum you will see a new type of organelle appear in my cell. It is called a lamellar granule. These are membrane bound organelles that first appear in the spinosum layer and are more prevalent as I morph into a stratum granulosum cell which is the next stage on my journey. Once I reach this granular layer the lamellar granules will secrete the precursors to the stratum corneum barrier lipids that will fill the intercellular space of the outermost epidermal layer. Lamellar granules contain glycoproteins, glycolipids, phospholipids, sterols and several enzymes. At first they assemble in the outer edges of my cell cytoplasm then cluster in vesicle like pockets of the extracellular space before I release them. Once outside the cell they remodel themselves into membrane like structures called lamellae that are found predominantly between the stratum granulosum and stratum corneum layers. Eventually, lamellar granule enzymes convert the precursor barrier lipids into lipids that coat the stratum corneum cells and provide a barrier to skin permeation. In the very outer layers of the stratum corneum the enzyme cholesterol sulfatase modifies the lipids, which assists not only in proper hydration of the epidermis, but in the desquamation process itself. The absence of this enzyme in lamellar granules corresponds with a loss of intercellular lamellae and a failure of the stratum corneum cells to slough— a condition known as retention hyperkeratosis. A horrible fate mind you.
So now you know the entire story of the lamellar granules. Since there’s more to tell you about the granulosum layer lets go back a stage.
As a cell in the stratum granulosum I have lamellar granules and a new type of structure called the keratohyaline granule. These are actually what gives this layer the name, stratum granulosum. Keratohyaline granules are protein dense granules comprised of profilaggrin and keratin filaments. Profilaggrin is a precursor of filaggrin which is thought to make up the matrix protein that promotes aggregation of keratin filaments. It is often referred to as filament aggregating protein because it cross-links keratin filaments, providing strength and structure. Interaction of these two proteins is important for normal epidermal structure and function.
As with all maturing processes, life is becoming extremely structured for me now. There is an abrupt transition from the moment I stop being a stratum granulosum cell to my emergence as a stratum corneum cell or corneocyte. Amazingly, when I was a granular cell not only could I synthesize and modifiy my proteins which were required for keratinization, but I was also instrumental in my own self-destruction. The granules in my cell contain many enzymes, some of which destroy my cell organelles including my cell brain center, the nucleus. This is carefully programmed within me and is a necessary process for differentiation of the epidermis.
As my journey comes to an end I find myself an inhabitant of the stratum corneum (SC) layer. This is the outermost layer of the epidermis that provides mechanical protection and is the major barrier to water loss and permeation of environmental substances into the skin. My role here is very simple-to protect you! The thickness of the SC varies depending on the part of the body; it may be 10 cells thick on your upper arm or hundreds of cell layers thick on the soles of your feet or palms. In additional to regional variation, the thickness of the SC varies with your age, sex, and disease or skin condition. We are often referred to as corneocytes when we reach this stage. I am the largest of all of the keratinocytes but I have a flattened shape now. I have no nucleus or any visible cellular contents or organelles. I am now filled with keratin protein embedded in a fillagrin rich matrix. My shape, structure and composition changes depending on my location in the Stratum Corneum layer; when deeper in the epidermis, a region often called the stratum compactum, I am plumper with a more fragile cell covering or envelope. By the time I reach the outermost SC, called the stratum dysjunctum, I will have developed a more rigid envelope and have fewer desmosomes, or points of cell attachment. This is the result of proteolytic enzymes that facilitate natural desquamation or exfoliation.
Overall the arrangement of corneocytes in the SC is similar to that of a brick wall with brick and mortar construction. The SC is composed of protein rich corneocytes (representing the bricks) embedded in a lipid matrix extruded from the lamellar granules (the mortar). Often one hears of the SC referred to as “the dead layer” of the skin; this merely means that the SC cells no longer synthesize proteins and are not responsive to cellular signaling. Trust me, we are not really dead, we have retained some metabolic functionality and we are fully functional in our capacity as protective corneocytes.
One of my protective functions now that I am a stratum corneum cell is to prevent dehydration of the skin by reducing transepidermal water loss (TEWL). I have two major assistants that allow me to perform this function; they are the natural moisturizing factor (NMF) and lipids. The NMF is the result of a combination of amino acids and breakdown products of fillagrin. It is made up of very water-soluble chemicals which facilitates its holding large amounts of water in the skin. It also provides an important aqueous environment for enzymes of the SC. The importance of the NMF is very apparent when one considers the skin condition known as Ichthyosis vulgaris,. In this condition, patients lack a normal NMF and display severe dryness and scaling of the skin. Normal skin when exposed to harsh cleansers such as soap will also display reduced levels of NMF as does the skin of many elderly patients.
I also have lipids available to me to help control TEWL. My arsenal consists of triglycerides, fatty acids, squalene, wax esters, diglycerides, cholesterol esters and cholesterol. Not only do these lipids help control TEWL, but they help prevent the entry of water soluble environmental agents and harmful bacteria into the skin. Of course the lipids of the SC are affected by your age, genetics, seasonal influences, and diet. Any deficiency in these lipids results in dry skin due to increased TEWL.
Skin lipids are produced in and extruded from my lamellar granules or are produced and excreted from the sebaceous glands associated with the hair follicle. The amount of sebum produced by the sebaceous glands has been demonstrated to be influenced by hormones in the body. The major lipids that help control TEWL are ceramides, cholesterol and fatty acids. Several years ago it was suggested that ceramides were the most important lipids for maintaining water balance in the skin. Today it is believed that no one lipid is more important than another. It appears that it is the ratio of ceramides, fatty acids and sterols that is important.
All in all it has been any where from 28 to 42 days on average since my birth as a basal daughter cell. I have endured numerous structural and chemical changes during my metamorphosis and hopefully I have done my job to protect you. My time has come to leave you. I have endured the process of keratinization only to now encounter desquamation. You probably won’t even notice me, as most of us will be shed as individual cells or small clusters that are invisible to the naked eye. From the time I was born my internal clock has been programmed to run its course. And now that time is here. I hope I have served you well.
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