Natural moisturizing factor (NMF) emulator

Why “emulate” and not simply copy?

Some very important components in the skin are composed of chemicals and cell parts that can’t be sourced. An example? Dead cells in the stratum corneum. But when the skin barrier is damaged (and it happens too frequently in life) we must be able to fix it, temporarily or not, and human cells are not an approved (or desirable) ingredient.

Emulating natural substances: the natural moisturizing factor
The horny layer (stratum corneum) of the epidermis has no live cells but is biochemically very active. The components of the natural moisturizing factor (NMF) is a mixture of amino acids and their derivatives with a high binding capacity for water. NMF keeps the skin hydrated, but frequent washing will remove this valuable resource. Skin Actives offers an NMF emulator that can be used to prevent and alleviate skin xerosis and other skin problems caused by the loss of NMF.

The epidermal stratum corneum

Figure: The layers of the epidermis


The stratum corneum (SC) is the outermost layer of the epidermis in the skin. Its main functions are preventing desiccation and the uptake of hazardous chemicals. Healthy SC should be soft and pliable and tolerate deformation from physical strain and stress. The SC can be seen as a complex biomaterial that has to fulfill different requirements in an environment with low relative humidity.
SC consists of dead epidermal cells, also known as corneocytes, embedded in an extracellular multi-lamellar lipid matrix. The corneocytes are filled with keratin arranged as coiled coils, associated with filaments classified as intermediate filaments due to their size and diameter, which correspond to approximately 7–10 nm. These filaments are further embedded in a protein matrix and enclosed by a cornified envelope consisting of crosslinked proteins, including involucrin, loricrin, small proline-rich proteins, and ceramide lipids.
Corneocytes, with their keratin filaments and cornified envelope, give the skin its mechanical properties of being simultaneously strong and elastic. They are embedded in a multi-lamellar lipid matrix composed of long-chain ceramides, fatty acids, and cholesterol.

What does NMF do?
Osmolytes are small polar compounds that decrease water’s chemical potential and can protect the SC from severe drying by dampening the molecular responses to changes in hydration.
In healthy skin, osmolytes are naturally present, commonly called the natural moisturizing factor (NMF). The NMF consists of a combination of small polar compounds derived from the protein filaggrin in the corneocytes, sweat constituents, and triglyceride turnover occurring in the sebaceous glands. The NMF mixture can make up for up to 10% of the dry weight of the corneocytes and consists of different amino acids and amino acid derivatives, such as pyrrolidone carboxylic acid (PCA), urocanic acid (UCA), lactic acid, sugars, urea, glycerol and a variety of ions.
The water content in SC exposed to air with ambient humidity is relatively low (around 20 % wt/wt water). The water concentration will typically vary between the different SC regions but must be high enough to maintain enzymatic activity, which is essential for desquamation and skin regeneration processes.
The SC is regularly exposed to varying conditions in its surroundings in terms of relative humidity, direct exposure to liquid water, and moisturizing or skin care products, and these changes in the water activity surrounding the skin will also influence the water activity in the SC itself. Changes in hydration conditions will not only change the water content in SC, they can also lead to the melting of a small portion of the extracellular SC lipids and increased mobility in the terminal amino acids of the keratin filaments inside the corneocytes. The response in the molecular properties of SC lipids and proteins to the changes in hydration may, in turn, strongly affect the physiology of the SC, including barrier function and mechanical properties

The problem
Decreased NMF has been associated with skin problems such as winter xerosis, atopic dermatitis, and severe skin dryness. The NMF composition has also been shown to influence the macroscopic properties of SC; SC elasticity decreased upon the removal of NMF and was regained by adding either basic or neutral amino acids. SC permeability was shown to increase with the addition of osmolytes such as urea or glycerol. When the skin is washed frequently or soaked in water, water-soluble NMF compounds are lost.

Why emulate and not copy NMF?
The body solves problems by transforming enzymatically the raw materials it has available. When we look at the “solutions” the body has designed, like NMF, ceramides in the epidermis, or vernix caseosa (the waxy coat that covers newborns), we should try to understand how they work. The functionality is not tied to the identity of the chemicals, and we aim to replicate the functionality or improve on it.

Vernix, whose function is to “waterproof” the baby’s skin in the uterus, has a variable composition but comprises sebum, cells that have sloughed off the fetus’s skin and shed lanugo hair.  Ceramides are made by the epidermis using the fatty acids present in the lower layers of the epidermis. NMF is mainly derived from the proteolysis of filaggrin, one of the many processes that occur while the epidermis’ live cells are converted into dead corneocytes.

Once we understand how the NMF, ceramides, etc., do their job, we can start looking at more effective ways of emulating them. For example, ceramides are expensive to source from acceptable materials (brains are not an acceptable source!) that will do a similar or better job without the expense, both monetary and ecological.

We can improve on natural solutions because we have so many natural chemicals at our disposal. In this case, we added amino acids that the skin can use to make new proteins.

What we want in our Skin Actives NMF
• Glycerin (glycerol)
• Hyaluronic acid or other jellifying polymers
• Sea kelp bioferment
• A mix of amino acids suitable for the skin

References
Robinson M, Visscher M, Laruffa A, Wickett R. Natural moisturizing factors (NMF) in the stratum corneum (SC).(2010) I. Effects of lipid extraction and soaking. J Cosmet Sci.61:13-22. PMID: 20211113.
Gunnarsson, M., Mojumdar, E. H., Topgaard, D., & Sparr, E. (2021). Extraction of natural moisturizing factor from the stratum corneum and its implication on skin molecular mobility. Journal of Colloid and Interface Science. doi:10.1016/j.jcis.2021.07.012
E. Candi, R. Schmidt, G. Melino (2005) The cornified envelope: a model of cell death in the skin. Nat. Rev. Mol. Cell Biol., 6: 328-340, doi:10.1038/nrm1619
I.R. Scott, C.R. Harding, J.G. Barrett (1982) Histidine-rich protein of the keratohyalin granules: Source of the free amino acids, urocanic acid and pyrrolidone carboxylic acid in the stratum corneum, Biochimica et Biophysica Acta (BBA) – General Subjects 719: 110–117. doi: 10.1016/0304-4165(82)90314-2.

DISCLAIMER: These claims have not been evaluated by the FDA and are not intended to diagnose, cure, treat, or prevent any disease.