The skin is subject to constant mechanical stresses, including stretch and compression due to body movement. In the skin the extracellular matrix (ECM) provides the structural support, which allows the skin to withstand external forces without compromising its integrity and function. Skin behaves as a viscoelastic material, combining viscous responses (slow deformation under stress) and elastic responses (recovery of original shape post-deformation).

This mechanical behavior is primarily attributed to the dermis, which contains a dense fibrous ECM composed mainly of collagen (77%) which confers skin tensile strength and elastin fibers (4%) which provide elasticity. These fibrillar proteins are embedded in a hydrated matrix of glycosaminoglycans (GAGs), which contribute to shock absorption and hydration maintenance. In parallel, the epidermis, through its stratified layers of keratinocytes, provides an additional degree of mechanical rigidity, particularly evident when comparing tensile and indentation measurements. Beyond passive mechanical support, skin cells are active mechanosensors. They detect and respond to their physical environment through mechanotransduction pathways that regulate processes such as migration, proliferation, and differentiation. This sensitivity is critical for maintaining tissue homeostasis and coordinating repair following injury.

Age-related changes in skin illustrate the consequences of altered mechanical balance. With aging, collagen fibers become excessively crosslinked via glycation, increasing rigidity while decreasing elasticity. Elastin degradation and disorganized ECM architecture further compromise mechanical performance. These alterations highlight the importance of evaluating ECM composition, organization, and functional integrity under controlled in vitro conditions.

In vitro analysis of skin mechanics typically involves characterizing ECM structure, protein localization, organization, degradation in relation to the mechanical resistance of the skin. Key targets include collagen fiber synthesis, degradation and alignment, elastin fiber integrity, fibrillin microfibril organization (Fibrillin-1, Fibrillin-2), matrix metalloprotease and GAG content and distribution as well as cell contractile capacity.

What are the major components of the ECM that can be studied?

1. Collagens, backbone of the tissue architecture, are categorized into 3 main sorts:

• fibril-forming collagens (types I, II, III),
• network-forming non fibrillar collagens (type IV), that composed a non-fibril network.
• fibril-associated collagens (types IX, XII), and others (type VI).

5. Glycosaminoglycans (GAGs) are polysaccharides and help to keep water. The diversity of proteoglycans and their high interaction with growth factors and their receptors provides structural basis for a multitude of biological functions. They are divided in four groups: hyaluronic acid, keratan sulfate, chondroitin/dermatan sulfate, andheparan sulfate.
6. The laminins forms networks that remain in close association with cells through interactions with cell surface receptors.
7. The role of the fibronectin fibrils is the attachment and migration of cells, like a “biological glue”.
8. Elastin fibers confer elasticity and through cross-links with tropoelastin mediated by LOX finally form desmosine or isodesmosine.

Among advanced tools for such analysis, Atomic Force Microscopy (AFM) has emerged as a powerful technique. AFM is a scanning probe method that provides nanoscale resolution for both topographical imaging and mechanical measurements. It can map surface roughness and elasticity by performing localized force spectroscopy, acting effectively as a nanoindenter. AFM also enables simultaneous mechanical and morphological analysis, especially when combined with optical microscopy such as confocal microscopy. This dual capability allows researchers to directly correlate biomechanical behavior with biomolecular features. For example, AFM coupled with X-ray diffraction (SAXS) allows Imaging and in situ characterization of the nanostructure of dermal collagen fibers and networks. AFM has been used to assess the strength of cell–matrix interactions, cell-generated traction forces, and the mechanical properties of ECM networks, including collagen and fibrillin structures.

In vitro assessment of the mechanical components with tools like AFM provide a precise platform for exploring the structural and functional complexity of skin tissue and offer an interesting insight into the efficacy of cosmetic formulations and active compounds.

In conclusion, this incredible network that represents the skin extracellular matrix, substrates for matrix metalloproteinases (MMPs), stocks bioactive fragments, and adhesive proteins. It is also modulated by exogenous environment. The own biochemical properties of the ECM can be studied in many ways through the analyse of its various components and their interactions and constitute a “gold” support to substantiate ingredients and finished product claims.

Contact

Anne Charpentier

CEO & Founder

www.skinobs.com

References

1. C. Biggs et al, Mechanical Forces in the Skin : Roles in Tissue Architecture, Stability, and Function, J. Invest. Dermatol. (2019) 1–7.
2. E. Tracy, et al. Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound., Adv. Wound Care. 5 (2016) 119–136.
3. Kalra, et al, Mechanical Behaviour of Skin: A Review, J. Mater. Sci. Eng. 5 (2016) 1–7.
4. Godwin ARF, et al. The role of fibrillin and microfibril binding proteins in elastin and elastic fibre assembly. Matrix Biol. (2019) 84:17-30.
5. John T. Connelly et al. Research Techniques Made Simple: Analysis of Skin Cell and Tissue Mechanics Using Atomic Force Microscopy, J Invest Dermatol, (2021) 141: 8: 1867-1971
6. Wenguang. Modelling methods for In Vitro biomechanical properties of the skin: A review Biomed Eng Lett. (2015). 5:241-250