May 10, 2021 | Jerry Bergman

Complex Design Seen in Human Skin

Skin: An Organ Once Thought to Be Simple
Is Now Shown to Be Far More Complex;
Two New Discoveries Illustrate Intelligent Design

 by Jerry Bergman, PhD

Most human body organs, once damaged, cannot regenerate. Two well-known exceptions include the liver and skin. One could lose half of the liver and it will regenerate without a problem in most healthy persons. In fact, new research has shown that the skin also is turning out to be far more complex than believed just a few years ago. For example, new treatment systems have been developed to coax the skin to repair itself in the way it was originally designed to heal. One new study involving mice used an acellular product derived from platelets to stimulate skin regeneration.[1] Platelets have been long known to play a role in skin healing, specifically platelet-derived growth factor (PDGF). Another study explains why skin doesn’t leak.

Coaxing Skin to Repair Itself

Injury causes platelets to release PDGF and transforming growth factor beta (TGF-b). These attract neutrophils (tissue-healing white blood cells) which scavenge for bacteria and foreign debris at the injury site. Platelets also cause the release of macrophages which are critical mediators of wound healing. The body normally uses this system in response to injury, but sometimes it is less functional, or even non-functional. Reasons include mutations that damage the genes which construct the system, or diet deficiencies, disease or other problems.

Figure 1. Diagram of human skin showing the three layers and the gland system.
From Wiki Commons.

New Therapy Recovers the Skin’s Design

Faults in skin repair can be compared to failures in sugar processing. To treat Type I diabetes, insulin can be manufactured commercially using bacteria and injected into the patient. Similarly, the technique used by the Mayo Clinic to heal skin wounds, as mentioned above, stimulates a body’s natural system to facilitate skin repair. The clinic designed an extracellular vesicle that functions like a truck to deliver cargo produced in one cell to another cell. The vesicle targets the tissues that need repair. Its cargo is an exosomal product called PEP derived from platelets. The vesicles deliver PEP into damaged cells. The technique worked. It resulted in the restoration of normal scar-free skin. Remarkably, it also restored hair follicles, sweat glands, and the production of skin oils to achieve normal hydration. Not only was the wound closed, but also the proper blood supply to the injured tissue was restored.

The cargo derived from platelets, called PEP (purified exosomal product), can be biomanufactured for clinical applications. This new method creates the potential for major advancements in treatments of ischemic wound damage (due to blocked blood flow) and plastic surgery. The technique is especially effective for ischemic wounds caused by clogged or blocked arteries that prevent nutrients and oxygen from reaching the skin for normal maintenance and repair.[2] Chronic ischemic wounds are common in patients with diabetes, pressure ulcers, hardening of arteries, and radiation therapy. Standard treatments used now often cannot fully close the wound, leading sometimes to amputation of a limb. Clinical tests for using purified PEP for wound healing are now underway.

Figure 2. Diagram of human skin showing in more detail the gland system.
From Wiki Commons.

Additional Research Explains Why our Skin Doesn’t Leak Fluids

Skin is constantly shedding cells, yet does not leak fluids. Why is that? Leakage would be lethal. This mystery has baffled researchers for decades. The three main skin layers of humans are the outer layer, the avascularized epidermis, the middle layer, containing the stratum granulosum, and the bottom layer, the subcutaneous fat, or hypodermis (see Figures 1 and 2). The epidermis is made of a thick outer barrier of dead epidermal cells, which are constantly shed. This outer layer is the main skin barrier which gives skin its color. It contains specially designed immune cells. In the dermis below the epidermis, the stratum granulosum is constructed out of a single layer of cells. Although much thinner than the other two layers, it serves as the fluid barrier.

Cells called keratinocytes divide at the lowest epidermis level. These new cells gradually push to the top layer where they are sloughed off by normal living activities. When the top dead layer, the stratum corneum, breaks away from the epidermis and falls off, it makes room for the newer cells growing below.

Amazing FactsIt takes about a month for new cells to move from the bottom to the top layer in most humans. Consequently, in a month a completely new epidermis is produced. A healthy adult sheds an estimated 200 million skin cells every hour.[3] During a 24-hour period, a person loses almost five billion skin cells, which becomes the main composition of common house dust.  It “has been a challenge for scientists to explain how this colossal shedding process can occur without there being a break in the skin barrier.”[4]

How Geometry and Proteins Create a Fluid Barrier

Scientists at Imperial College London found in 2016 that the shape and binding capability of epidermal cells helps explain how skin maintains a barrier even when it is shedding. Their work helps explain the “paradox of how we can shed them without compromising our skin’s integrity. It could also help us to understand what happens when it [this layer] forms incorrectly, which could lead to conditions like psoriasis and eczema.”[5] (See Figure 4.)

Figure 3. Space-filling tetrakaidecahedron. Often called Kelvin’s cell. From Wiki Commons

The shape of cells in the stratum granulosum combined with their ability to temporarily ‘glue’ themselves together helps explain how they form this strong barrier. The shape of these cells is a flattened version of a tetrakaidecahedron, a 3-D solid with 14 sides (see Figure 3.). The Yokouchi study determined the shape by studying skin cells with both confocal and two-photon excitation microscopy (TPEF or 2PEF). Historically, the great Scottish physicist William Thomson, better known as Lord Kelvin (see our biography of Lord Kelvin) concluded in 1887 that the flattened tetrakaidecahedron (f-TKD) was the best design for packing equal-sized objects together to fill a space with minimal surface area.

The Yokouchi study also found that this was by far the best design for stratum granulosum skin cells. Any other design would not achieve an effective liquid barrier when shedding skin cells. Both processes are required for life. The tight junctions are incredibly narrow areas between tessellating skin cells that are virtually impermeable to fluid.[6]

The stratum granulosum’s unique tetrakaidecahedron design forms a very tight, cohesive bond with the surrounding epidermal cells because the rectangular and hexagonal sides enable one cell to tightly connect to its neighboring cells. These cells also manufacture proteins that function as temporary ‘glue’ to bind the cells together. They form what is known as  ‘tight junctions’ – connections that prevent water leakage. When new cells push the older cells upwards toward the skin surface, the older cell’s tight junctions are loosened. The new cells form tight junction barriers in the cell sheet, maintaining the tight junction design without interruption.[7]

Figure 4. Eczema on the arms. From Wiki Commons.

Malfunctions in stratum granulosum tight-junction design (caused, for instance, by genetic mutations) may contribute to eczema. This condition occurs when a compromised skin barrier permits bacterial infiltration, then inflammation. The resulting irritation prompts skin scratching, resulting in further infection. Failures in the interlocking barrier between cells may also help explain the overproduction of epidermal cells that occurs in psoriasis – a condition characterized by patches of thick skin on the surface.

Summary

Skin is our body’s largest organ. It is vital that we completely understand its design. This will enable us to better deal with it, when it malfunctions, such as in eczema or psoriasis. Understanding what went wrong will help us learn what to do to repair it.[8] The problem is not the design. The problem is mutations, poor health, malnutrition or injury. The two recent studies evaluated here document a superior, ingenious design in skin. What leads to disease are mutations that prevent the design from functioning properly.


References

[1] Mayo Clinic, 2021. Preclinical discovery triggers wound healing, skin regeneration. 28 April.

[2]. Moran, Steven. et al. 2021. TGF-β donor exosome accelerates ischemic wound healing. Theranostics 2021; doi:10.7150/thno.57701.

[3] Yokouchi, Mariko et al., Epidermal cell turnover across tight junctions based on Kelvin’s tetrakaidecahedron cell shape. eLife, 2016; 5 DOI: 10.7554/eLife.19593m.

[4] Smith, Colin. 2016. New insights into skin cells could explain why our skin doesn’t leak. Imperial College London, 29 Nov.

[5] Smith, 2016.

[6] Crew, Sec. 2018. Scientists Have Figured Out Why Human Skin Doesn’t Leak. Science Alert. https://www.sciencealert.com/this-is-why-human-skin-doesn-t-leak-biology.

[7] Yokouchi, et al. 2016.

[8] Yokouchi, et al. 2016.



Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.

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