380 JOURNAL OF COSMETIC SCIENCE
into the body. The brick and mortar structure of the SC, proposed almost half a century
ago,1,14 has been investigated in detail over the years. See Figure 1 for a schematic of the brick
and mortar structure.5 The SC consists of corneocyte bricks embedded in a lipid matrix.3
Covalently bonded lipids attached to the corneocyte envelope compatibilize the brick with
the surrounding lipids. Corneocytes are further attached together by desmosomal proteins.
The proteins within the corneocyte bricks exist as crosslinked keratin and low molecular
weight natural moisturizing factors (NMFs) that help hold water within the SC.
The SC, which was thought to be a dead layer of skin about half a century ago, is now
recognized to be a hot bed of enzyme activity and biological processes.3,5,15 One such
process is the desquamation of skin layers in a layer-by-layer fashion, losing at least one
layer every day, with a fresh layer being exposed regularly. The overall corneum turn-over
period in normal skin is about four weeks. For this to happen, the desmosomal linkages
need to be degraded as the SC layers move to the surface, and this is accomplished by
proteolytic enzymes in the SC. The other two important enzyme driven processes in the
epidermis include the breakdown of filaggrin protein into NMFs and the conversion of
glucosylceramides into ceramides, a key lipid involved in the matrix bilayer lipids. Both
skin pH and hydration affect these enzymatic processes.
The matrix lipids that surround the corneocytes consist of ceramides, cholesterol, and
fatty acids—approximately in a 1:1:1 molar ratio.4 The composition and the possible
structural organization of these bilayer lipids have been discussed in detail over the past
three decades.4,16–18 Ceramides are two-tailed lipids, and depending upon the nature of the
headgroup and the tails, 20 classes of ceramides have been identified in the human SC.15,19
Similarly, fatty acids have also been found with chain lengths, mainly from C20 to C28,
and even low levels of C32.20 Bouwstra and coworkers have investigated the organization
Figure 1. Refined “bricks and mortar” representation of the structural components of the SC. Reproduced
with permission from A. V. Rawlings and R. Voegeli, Stratum corneum proteases and dry skin conditions,
Cell Tissue Res (2013) 351:217–235, DOI 10.1007/s00441-012-1501-x.5

381 The Human Stratum Corneum
of SC lipids using isolated SC, lipids extracted from SC, and model lipids. Techniques
such as X-ray diffraction have shown that the lipids exhibit one long periodicity around
13 nm (Long periodicity phase – LPP) and a second one around 6 nm (short periodicity
phase SPP).4,17 Based on these findings, Bouwstra and coworkers have proposed a sandwich
model of lipid organization that includes a crystalline phase and a fluid phase in the
bilayer lipids with stacking of alternating fluid and crystalline phases. The domain mosaic
model of SC lipid organization proposed by Forslind depicts the simultaneous presence of
both a crystalline and a liquid crystalline lipid phase.16 The fluid phase is thought to be
discontinuous in the direction of depth this organization allows flexibility within the lipid
layer without compromising permeability barrier properties of the SC. In contrast to the
sandwich model and the domain mosaic models, Norlen has proposed a gel-phase model
in which SC lipids are suggested to form a single and coherent gel-phase in the lower half
of the SC.18 While one can debate the merits of each of these models, it seems reasonable
that the presence of a crystalline phase along with a fluid phase seems reasonable since such
a structure can manage stress better without cracking compared to a rigid gel structure.
These two-phase models also can account for the presence of both the LPP and SPP phases
in the bilayer.
Within the SC lipid phases, they exhibit orthorhombic, hexagonal, or fluid packing as
shown in Figure 2.4 The existence of such phases has been confirmed by ATR/FTIR
techniques.9,12 The orthorhombic packing is the tightest of these structures, with the least
water permeability compared to others.4 It has been shown in in-vivo studies that trans
epidermal water loss (TEWL) decreases with increases in the fraction of orthorhombic
fraction of the bilayer lipids.12 Note that even in healthy skin, the proportion of
orthorhombic fraction increases with increase in depth into the SC.21–23 This may be due to
Figure 2. Stratum corneum lamellar phases and various lateral packing possibilities. Reproduced with
permission from Bouwstra, J., and Gooris, G. The Open Dermatology Journal. 4, 10–13 (2010).4