ABSTRACT
Experiments performed in the early 1950s in which the effects of organic
solvents on permeability of the skin were studied implicated stratum corneum
lipids in the function of the permeability barrier (Berenson and Burch, 1951;
Blank, 1952). However, little further progress was made until 1973, when two
breakthroughs were reported. Through the use of electron dense water soluble
tracers, Squier (1973) was able to demonstrate by transmission electron
microscopy that the permeability barrier starts at the bottom of the stratum
corneum, where the contents of the lamellar granules are extruded. These
studies also indicated that all layers of stratum corneum contribute to barrier
function. In this same year, Breathnach et al. (1973) demonstrated by freeze
fracture electron microscopy that the intercellular spaces of the stratum
corneum contain multiple stacked, broad lipid sheets. These findings were
further elaborated by Elias and Friend (1975). In the scenario that emerged from
this body of work lipids accumulate in lamellar granules, and are extruded into
the intercellular spaces in the upper granular layer. After extrusion, the short
stacks of lipid lamellae are transformed into multiple broad lipid sheets which
fill most of the intercellular spaces throughout the stratum corneum. It is this
lamellar lipid in the intercellular spaces that determines the permeability of the
stratum corneum.