Research ArticleHEALTH AND MEDICINE

Morphology and composition play distinct and complementary roles in the tolerance of plantar skin to mechanical load

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Science Advances  09 Oct 2019:
Vol. 5, no. 10, eaay0244
DOI: 10.1126/sciadv.aay0244
  • Fig. 1 The load-bearing structures of skin.

    (A) The stratum corneum consists of terminally differentiated keratinocytes embedded in a lipid matrix and provides the contact surface for external mechanical loads. (B) In the viable epidermis, mechanical loads are borne directly by keratinocytes. Desmosomes provide mechanical junctions between neighboring cells, while keratin filaments provide the cell’s internal structural support. (C) The epidermal-dermal junction (EDJ) mechanically connects the dermis to the epidermis via the intermediate layer, the lamina densa. Anchoring fibrils connect the keratinocytes of the epidermis to the lamina densa (or basement membrane), and likewise, fibrils loop down from the lamina densa into the extracellular matrix (ECM) of the dermis. (D) Loads in the dermis are borne by extracellular matrix consisting of structural fibers, such as collagen and elastin, embedded in a ground substance consisting of glycosaminoglycans, proteoglycans, and water. Dermal fibroblasts create and maintain this matrix.

  • Fig. 2 Morphology and composition of plantar skin.

    (A) H&E-stained sections indicating the morphological differences between plantar and nonplantar skin, including a thicker stratum corneum (SC) and viable epidermis (VE) in plantar skin (n = 414 and 1440 for stratum corneum and viable epidermis, respectively). There is greater interdigitation between the epidermis and dermis (D) in plantar skin as measured by the arc-chord ratio (n = 30 measurements). (B) Immunofluorescence imaging of skin sections shows that the dermis of plantar skin contains more capillaries [as indicated by collagen IV (COL IV) staining] compared to nonplantar skin. The epidermis of plantar skin uniquely expresses K9, while there is also higher expression of DSG1 in the epidermis and less LAM (laminin) and COL IV at the basement membrane. (C) SHG images showing collagen organization in the dermis reveal that the collagen in plantar skin is arranged in thicker bundles compared to nonplantar skin, and there are a greater proportion of thick fibers in plantar skin (n = 36 measurements). SHG signal intensity is significantly higher in plantar skin than in nonplantar skin (n = 14 measurements). Thick collagen fibers (asterisks) run parallel to the EDJ (dashed lines) in plantar skin. Scale bars, 200 μm. Reported P values are based on two-sided Student’s t tests.

  • Fig. 3 Plantar skin resists deformation.

    (A) Uniaxial compression and simple shear tests on ex vivo skin. Deformation was measured as the initial strain after compression of 10 kPa (top) and shear of 2 kPa (bottom). Tests are from two patients, with three samples from each anatomical location. Loads were maintained for 300 s, and final deformation was measured as creep strain. (B) AFM indentation experiments using a spherical (4 μm) tip on cryostat sections of skin. (C) High-resolution force mapping using a sharp AFM tip shows that the change in Young’s modulus with depth is more gradual in plantar skin. Two-dimensional (2D) stiffness maps (50 μm wide) are shown alongside depth-specific data. Black lines represent LOESS regression fits of the data, while color intensity represents the spread of elastic moduli at each depth. ***P < 0.001, **P < 0.01, two-sided Student’s t test.

  • Fig. 4 Plantar skin experiences less deformation than nonplantar skin under load.

    (A) Shear strains in nonplantar skin (top left) and plantar skin (bottom right) under equal compressive and shear load, with models representing plantar morphology, but nonplantar composition and vice versa. Contour plots show the highest shear strains induced in the dermis of nonplantar skin. (B) Kernel density estimates of shear strains in the dermis and (C) viable epidermis with effect size relative to nonplantar skin. (D) Three knockout models were created from the original plantar model in which the material properties of the stratum corneum (left), viable epidermis (middle), or dermis (right) were reduced from plantar to nonplantar. (E) Kernel density estimates of shear strain in the dermis and (F) viable epidermis for each of the knockout models. Peak shear strains are statistically significantly different between all models in this analysis (P < 0.0001, two-sided Student’s t test) due to the very high number of sampling points (n = 5402 and 8845 for plantar and nonplantar models, respectively). Because the number of sampling points for these simulations is arbitrary, effect size is reported in this figure rather than statistical significance.

  • Fig. 5 Plantar skin morphology protects it from stress-induced injury.

    (A) Stresses induced in plantar (bottom right) and nonplantar skin (top left) under equal compressive and shear loads. Contour plots show the distribution of von Mises stresses in the skin. Plantar composition (via the material properties) was combined with nonplantar morphology (top right) and vice versa (bottom left). (B) Kernel density estimates showing the distribution of stress magnitudes in the dermis and (C) viable epidermis. Difference in peak stress (defined as 95th percentile value) between each model and nonplantar skin is also shown (lines indicate 95% bootstrapped confidence interval of the difference). (D) Knockout models of plantar skin were created by reducing the thickness of the stratum corneum to that of nonplantar skin or reducing the interdigitation between the epidermis and dermis. (E) Kernel density estimates of the stress in the dermis and (F) viable epidermis for knockout models. Difference in peak stress is presented relative to plantar skin. Peak von Mises stresses are statistically significantly different between all models in this analysis (P < 0.0001, two-sided Student’s t test) due to the very high number of sampling points (n = 5402 and 8845 for plantar and nonplantar models, respectively). Because the number of sampling points for these simulations is arbitrary, effect size is reported in this figure rather than statistical significance.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/5/10/eaay0244/DC1

    Table S1. Antibodies used.

    Table S2. Shear moduli based on rule-of-mixtures analysis.

    Fig. S1. Histological analysis.

    Fig. S2. Mechanical testing of skin.

    Fig. S3. Constructing finite element models of the skin.

  • Supplementary Materials

    This PDF file includes:

    • Table S1. Antibodies used.
    • Table S2. Shear moduli based on rule-of-mixtures analysis.
    • Fig. S1. Histological analysis.
    • Fig. S2. Mechanical testing of skin.
    • Fig. S3. Constructing finite element models of the skin.

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