How might stem cells influence Ms. Marvel and Mister Fantastic’s elastic skin?

New research from Belgian and UK researchers in Nature shows that skin growth is communicated by stem cells during stretching.

Kamala Khan (Ms. Marvel) and Reed Richards (Mister Fantastic)

Kamala Khan (Ms. Marvel) and Reed Richards (Mister Fantastic) are two Marvel superheroes with a bit in common. Although neither have yet to feature in the Marvel Cinematic Universe (Khan is scheduled to appear in her own Disney+ series and the film Captain Marvel 2 in 2022), both carry out most of their superhero activities in New York, and both have the power of elasticity or shapeshifting. 

Excessive stretching subjects their skin to large amounts of stress and strain, which would be detrimental for the integrity and healing of the skin of ordinary humans. Fortunately, both have accelerating healing factors that compensate for their elastic escapades. So how could Khan and Richards create new skin that’s functional and healthy when they stretch into unimaginable contortions? New findings from Belgian and UK-based researchers on mice have revealed that a group of stem cells in the epidermis help to initiate the growth of new skin cells once the skin is stretched. Information about this process could be hugely significant for reconstructive surgery and in the treatment of diseases that affect skin growth. Their work has been published in Nature

As a superpower, elasticity might seem like an impractical superpower, but it has proven quite useful to Kamala Khan, Reed Richards, and DC Comics’ Ralph Dibny (Elongated Man). Of the trio, Khan is the most recent addition to the superhero stable, having first appeared in Captain Marvel #14 in 2013. Khan frequently uses her shapeshifting power to increase the size of her arms, fists, and legs when fighting her foes, while Richards’ elasticity is even more extreme, allowing him to wrap himself around huge structures, as he did with the London Eye in Fantastic Four: Rise of the Silver Surfer

Evidently, Khan and Richards subject their bodies to immense stress and strain, and this can be testing for their bodies. However, extreme stretching is partially compensated by their superhero accelerating healing factors and enhanced cellular resistance to mechanical forces or perturbations. Their skin, in particular the upper layer which is known as the epidermis, experience extraordinary forces as their skin continually expands and contracts when fighting foes. 

The skin performs a number of key physiological functions such as preventing pathogens from entering the body, protecting against dehydration, and assisting in thermoregulation. The top part of the epidermis is known as the stratum corneum and is made up of dead keratinised cells. Through the process of desquamation, these cells are constantly shed, but they are replaced through the generation of new stem cells from the basal layer.

A multidisciplinary collaboration between researchers based in Belgium and the UK (with the lead author being Mariaceleste Aragona) took a closer look at how cell growth in the epidermis is affected by stretching. In experiments that were compliant with all relevant ethical regulations on animal research, the researchers placed a small amount of self-inflating hydrogel (often used in reconstructive surgeries for people) just underneath the skin of mice subjects. The hydrogels were pre-designed to expand to a certain shape and size.

Once the hydrogel had fully expanded, the researchers monitored the production of cells associated with keratin, a protein that is important for providing skin with mechanical resilience. The researchers then recorded a brief increase in stem-cell division and a thickening of the epidermal. In effect, the research reveals that more stretching leads to the growth (or proliferation) of more stem cells that can differentiate into more of the cell types needed to maintain the structure and integrity of the epidermis. In other words, more stretching leads to more skin cells in the epidermis!

The researchers also genetically modified some mice to study which genes are important for the creation of more skin cells. This involved switching off certain genes in mice, applying a minor stretch to their skin using the expanding hydrogel, and then studying the skin cell growth. For instance, the MAL gene, which provides the body with instructions to make the myelin and lymphocyte protein, was shown to influence cell response to stretching.

Importantly, the research demonstrates how the skin can maintain its protective function when expanding, which is good news for ordinary people and stretchy superheroes alike. Of course, the research poses additional questions. For example, how do other parts of the skin, such as the dermal layer below the epidermis, influence the formation of a new, larger epidermis after stretching? And does the dermal layer also expand to the same extent as the epidermis?

Although Kamala Khan and Reed Richards’ DNA differs from the DNA of an ordinary person, the cellular process through which they replace their epidermal layers is probably the same as that investigated by the Belgian-UK research team. Of course, the major difference is that the whole process is amplified for these elastic superheroes.

This fascinating piece of research might reveal how Khan and Richard’s fictional bodies could create more skin cells, but how do their bodies discard the extra skin after they relax their bodies and change back to their original, normal human form? Perhaps this is achieved via an enhanced cell shedding process that is activated by the shrinking of the skin. This means that Khan and Richards most likely leave large amounts of dead keratinised cells scattered over the area of any altercation with a devious villain. Tony Stark’s Damage Control might have to work overtime to cleanup those dead skin cells!

Full paper can be read at Nature.

You can also read a summary article about the paper here.