All SC lipids are important for barrier function of the skin but due to their unique properties and structure the ceramides have been of most interest in recent years. Ceramides constitute (on a weight basis) approximately 47% of the SC lipids (14). Given this diversity, together with the identification of new ceramides, a new nomenclature based on structure, rather than the original chromatographic migration characteristics, was proposed by Motta et al. (15). In this system, ceramides are classified in general as CER FB, where F is the type of fatty acid and B indicates the type of base. When an ester linked fatty acid is present, a prefix of E is used. Normal fatty acids (saturated or unsaturated), alpha-hydroxy fatty acids, and omega-hydroxy fatty acids are N, A, O respectively, whereas sphingosines, phytosphingosines, and 6-hydroxysphingosine are indicated by S, P, and H. Sphinganine (not previously classified) is proposed to be SP in this nomenclature
system. A novel long-chain ceramide containing branched chain fatty acids is also found in vernix caseosa (16). Typical structures of human ceramides are given in Figure 4. Newly identified ceramides have also been found attached to the corneocyte envelope (CE). In addition to ceramide A (sphingosine) and ceramide B (6-hydroxysphingosine), Chopart et al. (17) recently identified covalently-bound omega hydroxyl fatty acid containing sphinganine and phytosphingosine ceramides. These covalently-bound ceramides should now be named CER OS, CER OH, CER OSP, and CER OP.
Ceramides are synthesised from either glucosylceramides, epidermosides, or sphingomyelin. Epidermosides are glycated precursors of omega, hydroxyl-containing ceramides. The studies of Hamanaka et al. (18) have demonstrated that sphingomyelin provides a proportion of CER NS and CER AS whereas the glucosylceramides are precursors to ceramides and epidermosides are precursors to the covalently bound ceramides, together with CER EOS, CER EOH, and CER EOP.
It is the packing states, however, and not only the structures of the SC lipids that are important for barrier function. Lipids in vivo appear to exist as a balance between a solid crystalline state (orthorhombic packing) and gel (hexagonal packing) or liquid crystalline states. The orthorhombically-packed lipids are the most tightly packed conformation and have optimal barrier properties. However, a greater proportion of hexagonally-packed lipid conformations are observed in the outer layers of the SC (19). This is consistent with a weakening of the barrier towards the outer layers of the SC. It is believed that short chain fatty acids from sebum contribute to the crystalline to gel transition in the upper stratum corneum layers (20).
Bouwstra et al. (21) recently proposed a new sandwich model consisting of two broad lipid layers with a crystalline structure separated by a narrow central lipid layer with
fluid domains (Fig. 5). Cholesterol and ceramides are important for the formation of the lamellar phase, whereas fatty acids play a greater role in the lateral packing of the lipids. Cholesterol is proposed to be located with the fatty acid tail of CER EOS in the fluid phase. CER EOS, EOH, and EOP play an essential role in formation of the additional lamellar arrangements. The repeated distances were found to be 13 nm in dimension, composed of two units measuring approximately 5 nm each and one unit measuring approximately 3 nm in thickness. These repeat lamellar patterns were also observed by X-ray diffraction studies and were named the “LPP” and “short periodicity” (SPP) phases respectively.
Mostly hexagonal phases are also observed for total lipid mixtures in the absence of CER EOS. Equally no LPP phase is formed. Moreover, the importance of ceramide 1 or CER EOS in facilitating the formation of the LPP has been further elaborated by
SANDWICH MODEL
12-13 nm periodicity:
3 layers:
Crystalline lattice
Fluid phase
 |
 |
—’Crystalline lattice
alternating fluid and crystalline sublattices
Shear stress
is
located in the central lipid layer of this phase, and in this layer mainly unsaturated linoleic acid and cholesterol are present; (2) in the sublattice adjacent to the central layer a gradual change in lipid mobility occurs due to the presence of less mobile long saturated hydrocarbon chains; (3) only a small fraction of lipids forms a fluid phase in the SC, and therefore one can assume that this central lipid layer is not a continuous phase. (B) The liquid phase parallel to the basal layers of the lamellae facilitates transport and therefore communication between the desmosomes. Source: From Ref. 21.
understanding the influence of the type of fatty acid esterified to the omega-hydroxyl fatty acid (Fig. 6) (22). As a consequence, the LPP is seen mainly with linoleate-containing CER EOS, less with oleate-containing CER EOS and is absent if only stearate-containing CER EOS is present in the lipid mixtures. These studies indicate that for formation of the LPP, a certain fraction of the lipids has to form a liquid phase. If the liquid phase is too high (as with the oleate-containing CER EOS) or too low (as with stearate-containing CER EOS), the levels of the SPP increase at the expense of the LPP. It is important to remember in vivo that the fatty acid composition of CER EOS is highly complex but contains a large proportion of linoleic acid.
Changes to the composition of the SC lipids could, therefore, dramatically influence the condition of the skin. In this respect, using electron microscopy of tape strippings from the outer layers of normal healthy skin, Rawlings et al. (23) reported complete loss of lamellar ordering in the outer layers of the SC (Fig. 7). These results have been confirmed by Warner et al. (24) and more recently by Berry et al. (25).