Why serine levels matter for assessing skin condition

Assessing skin hydration and barrier health has largely relied on indirect methods—transepidermal water loss, corneometry, visual scoring. All of these provide a general picture but do not answer what is actually happening biochemically in the stratum corneum. Yet one specific molecule directly tracks hydration and barrier integrity: the amino acid serine. A new study published in Nature Communications focuses precisely on this molecule and on a way to measure it [1].

Serine is not just one of twenty proteinogenic amino acids. In the stratum corneum, it is the quantitatively dominant component of the natural moisturizing factor (NMF) — a complex of low-molecular-weight, hygroscopic substances that hold water inside corneocytes and keep the skin elastic. According to the authors, serine accounts for more than one-fifth of the entire NMF pool.

Beyond retaining moisture, serine participates in the biosynthesis of extracellular lipids for the epidermal barrier, in skin immune processes, and in regulating keratinocyte turnover. This is why its level is regarded not as an incidental marker but as an indicator that directly reflects the barrier's functional state: a decrease in stratum corneum serine is associated with atopic dermatitis, psoriasis, and xerosis (pathological skin dryness).
Notably, disruptions in serine metabolism are known outside dermatology as well — in oncological, metabolic, and several neurological conditions — underscoring the broader systemic significance of this amino acid.

How serine was measured before, and the limitations

Until now, reliably measuring skin serine content required laboratory methods — tape stripping (removing the stratum corneum with adhesive tape) followed by colorimetric or chromatographic analysis under controlled conditions. This approach is labor-intensive, time-consuming, equipment-dependent, and unsuitable for home monitoring or quick assessment in a practitioner's office.

Design and operating principle of the wearable biosensor

To address this challenge, the authors created a wearable system for non-invasive serine detection directly on the skin. The system consists of two parts: a disposable sensing patch and a portable electrochemical reader.

The patch includes a porous, ion-conductive polyvinyl alcohol hydrogel (optimal thickness 0.3 mm) through which serine diffuses from the stratum corneum, and an electrode coated with a molecularly imprinted polymer (MIP) — a polypyrrole layer bearing molecular "imprints" of serine. These "imprints" are microscopic cavities within the polymer structure whose shape and chemical groups precisely match the serine molecule. They are created during electropolymerization: serine is added to the solution while the polymer layer forms on the electrode, then washed out, leaving cavities of the corresponding shape in the material. These cavities subsequently and selectively bind serine molecules diffusing from the skin, following a "lock-and-key" principle, without responding to other substances.

The electrode is built in layers: a conductive carbon substrate is coated with Prussian blue nanoparticles that carry the electrical signal, topped with an electropolymerized polypyrrole layer containing the molecular cavities that selectively recognize serine.

The measurement principle relies on a change in the electrochemical signal upon serine binding. When the patch is applied to the skin, a concentration gradient drives serine to diffuse into the hydrogel and bind to the specific cavities in the MIP layer. This binding impedes electron transfer at the Prussian blue nanoparticles, which linear sweep voltammetry registers as a drop in peak current—the higher the serine concentration, the greater the signal decrease. A stable reading requires holding the patch on the skin for 5 minutes (the time needed to reach a quasi-steady state), after which it is inserted into the portable reader, and the result appears on the LCD screen.

Accuracy and reproducibility of the method

In testing, the system detected serine across a concentration range of 48 µM to 30 mM with a sensitivity of 2.85 µA per decade of concentration. Compared with reference methods—standard colorimetric assay kits and classic tape stripping—the correlation was 0.71–0.82, which the authors consider good agreement for a non-invasive method. The patch remains stable in air for at least 4 days and performs correctly across the physiological range of skin temperatures.

Practical applications: barrier monitoring and skincare efficacy assessment

The authors demonstrated the method's practical value in two scenarios.

The first involved monitoring skin recovery in atopic dermatitis: before treatment, the signal (and thus the serine level) in the lesion area differed from healthy skin, reflecting an impaired barrier. After one week of topical treatment, serine levels in the lesion rose but remained below those of healthy skin, indicating that continued therapy was needed. By the third week of treatment, serine concentration in the lesion area not only normalized but exceeded that of the intact skin. This trend paralleled the visible recovery of the skin (reduced erythema and flaking) and a decrease in transepidermal water loss—meaning the method can objectively and quantitatively track barrier-function recovery alongside clinical improvement, without requiring laboratory sampling.

The second scenario assessed the efficacy of a moisturizing skincare product containing moisturizing ingredients, including serine. The product was applied to a chosen area of forearm skin, while an adjacent area was left untreated for comparison. After application, serine levels on the treated area were statistically significantly higher (p<0.01) than on the untreated area. This difference was accompanied by both decreased transepidermal water loss and increased stratum corneum hydration, as measured by an independent commercial instrument—meaning the serine sensor data aligned with standard barrier-function assessment methods. The time course was also informative: serine levels rose rapidly and peaked around 2 hours after application, then gradually declined due to natural consumption, while remaining above baseline. The authors assessed measurement reproducibility across skin locations using coefficients of variation of 24.62% and 12.07%, an acceptable result given the inherent heterogeneity of skin as a measurement surface.

Together, both scenarios show that the method is suitable not only for diagnostics but also for quantitatively tracking the efficacy of both therapeutic and cosmetic interventions over time, without invasive procedures.

Study limitations

The technology is currently presented as a research prototype: the data come from a limited number of subjects and clinical cases, and the correlation range with reference methods (0.71–0.82), while good, is not a perfect match.

The study also does not provide a direct quantitative comparison of serine levels between "dry" and "normal" skin outside the context of a specific condition — comparisons were made between lesion and intact skin within the same patients.

Implications for skincare product development and use

For practitioners and skincare formulators, this work offers a fundamentally different level of control over care efficacy—not an indirect measure (based on sensation or overall hydration) but a targeted biochemical indicator of barrier condition.

In the future, such wearable sensors could objectively determine whether a product replenishes NMF and how long the effect lasts, personalize moisturizing formulations based on an individual's serine level, and monitor skin recovery dynamics in dermatological conditions linked to NMF deficiency. This opens a path toward more evidence-based, measurable assessment of cosmeceutical efficacy — replacing "before/after" visual scales with a concrete, trackable number.

Conclusion

This work thus demonstrates not only a new diagnostic tool but also a new way of understanding what "hydration" means at the molecular level, and how this molecular reality can be measured directly on the skin, without a laboratory.

Refernces

1. Yuan Y., Zhong B., Qin X. et al. An epidermal serine sensing system for skin healthcare. Nat Commun 2025; 16: 2681.
2. Handzlik M.K., Metallo C.M. Sources and sinks of serine in nutrition, health, and disease. Annu Rev Nutr. 2023; 43: 123–151.
3. Cork M.J., Danby S.G., Vasilopoulos Y. et al. Epidermal barrier dysfunction in atopic dermatitis. J Invest Dermatol 2009; 129: 1892–1908.
4. Kezic S., Kammeyer A., Calkoen F. et al. Loss-of-function mutations in the filaggrin gene lead to reduced levels of natural moisturizing factor in the stratum corneum. J Invest Dermatol  2008; 128: 2117–2119.
5. Min J., Sempionatto J.R., Teymourian H. et al. Skin-interfaced wearable sweat sensors for precision medicine. Chem Rev 2023; 123: 5049–5138.