Figure 1

(a) Schematic representation of the top two layers of skin: SC, the outermost layer, contains rigid corneocytes in a lipid matrix. Between corneocytes, the lipids show a periodic electron density pattern that is lost when the corneocyte walls are further apart [7]. A layer of lipids is covalently bound to the protein network of corneocytes forming the corneocyte bound lipid envelope (CLE). (b) CER is synthesized in SG, the layer immediately below SC. After synthesis, a sugar moiety is added to the head group and the resulting galactoceramides are released by endocytosis. Enzymes remove the sugar group to revert back to CER in the intercellular space [25].Reuse & Permissions

Figure 2

Schematic representation of selected SC lipid molecules: CER NP (b) differs from CER NS (a) by having an extra OH group. CER EOS (c) contains an additional linoleic acid conjugated to the fatty acid tail. Both CER (a)–(c) and FFA (d) have large polydispersity in the tail lengths. Cholesterol (CHOL) (e) is the only SC lipid also found in most fluid phospholipid membranes.Reuse & Permissions

Figure 3

Evolution of structure in $1:1:1$ molar ratio of CER, CHOL, and FFA SC lipids (cyan) with 30 wt % water (orange). (a) 0.5 ns after random placement of the molecules in a box of dimension $L=120\mathrm{nm}$, $L$ reduces slightly to 106 nm. Water and lipid molecules start to cluster. (b) At 0.9 ns the clustering is more pronounced and the density increases quickly ($L\sim 62\mathrm{nm}$). (c) At 1.1 ns the equilibrium density has been reached ($L\sim 18.8\mathrm{nm}$). The clumping of water is now more pronounced. (d) By 50 ns, the water molecules have arranged in a few large roughly spherical droplets, enclosed by coronas of lipid molecules [35].Reuse & Permissions

Figure 4

SC lipid (cyan) double bilayer (equimolar CER, CHOL, and FFA) with a thin layer of water (orange). There are no water molecules between the two bilayers. Nitrogen atoms in the head groups are shown as blue spheres. The simulation box is repeated once in both the $y$ and $z$ directions (the actual box dimension is indicated by dashed rectangle). (a) Lipid head groups in a small region across the thin water layer come closer to each other by natural fluctuations at around 20 ns [$L_x=18.1\mathrm{nm}$, $L_y=17.8\mathrm{nm}$, $L_z=12.2\mathrm{nm}$]. (b) The strong interaction between head groups pulls the leaflets closer (circled) [$t=40\mathrm{ns}$, $L_x=18.1\mathrm{nm}$, $L_y=17.8\mathrm{nm}$, $L_z=12.2\mathrm{nm}$]. (c) The water molecules evolve towards a cylindrical shaped region. Substantial rearrangement leads to a bilayer corona of lipid molecules around the water cylinder [$t=90\mathrm{ns}$, $L_x=18.5\mathrm{nm}$, $L_y=18\mathrm{nm}$, $L_z=12.1\mathrm{nm}$]. (d) The structure remains stable for the rest of the simulation (260 ns) [$L_x=16.3\mathrm{nm}$, $L_y=17.5\mathrm{nm}$, $L_z=14.1\mathrm{nm}$] [35].Reuse & Permissions

Figure 5

(a) Schematic representation of hypothetical CRW molecule used to mimic corneocyte wall. (b) Configuration of lipids (cyan) with continuous wall (not shown) along the $z$ boundaries. Nitrogen atoms in the head groups are shown as blue spheres. The box size is $15.4\mathrm{nm}\times 13.6\mathrm{nm}\times 21.7\mathrm{nm}$. (c) Configuration of lipids with CLE-mimic wall (lime) constructed with CRW molecules show layering, in contrast to continuous wall simulations. The two bilayers closest to the two walls are indicated by drawn lines. The box size is $13.6\mathrm{nm}\times 12.3\mathrm{nm}\times 28.8\mathrm{nm}$. Only 3 nm slices along the $y$ direction are shown in (b) and (c).Reuse & Permissions