This contribution summarises the results from a number of investigations un
dertaken in the spirit of the Domain Mosaic Model proposed by Forslind in 1
994. Atomic Force Microscopy (AFM) studies on the two-dimensional phase beh
aviour of some stratum corneum lipids revealed phase separation of the lipi
ds in the typical case and the ability of cholesterol to reduce the line te
nsion between phases. A theoretical model was developed describing the resp
onse of an oriented stack of polar lipid bilayers in the presence of a grad
ient in water chemical potential (water solution to humid air). The gradien
t gives rise to an inhomogeneous water swelling, and presumably to a liquid
crystal-to-gel transition in the lamellar region closest to humid air. Ski
n penetration enhancers such as Atone and oleic acid cause phase transforma
tions in lipid bilayer systems which may be relevant in the context of skin
permeation.