Water permeation through stratum corneum lipid bilayers from atomistic simulations

Abstract

Stratum corneum, the outermost layer of skin, consists of keratin filled rigid non-viable corneocyte cells surrounded by multilayers of lipids. The lipid layer is responsible for the barrier properties of the skin. We calculate the excess chemical potential and diffusivity of water as a function of depth in lipid bilayers with compositions representative of the stratum corneum using atomistic molecular dynamics simulations. The maximum in the excess free energy of water inside the lipid bilayers is found to be twice that of water in phospholipid bilayers at the same temperature. Permeability, which decreases exponentially with the free energy barrier, is reduced by several orders of magnitude as compared with phospholipid bilayers. The average time it takes for a water molecule to cross the bilayer is calculated by solving the Smoluchowski equation in the presence of the free energy barrier. For a bilayer composed of a 2:2:1 molar ratio of ceramide NS 24:0, cholesterol and free fatty acid 24:0 at 300 K, we estimate the permeability P = 3.7 × 10−9 cm/s and the average crossing time τav = 0.69 ms. The permeability is about 30 times smaller than existing experimental results on mammalian skin sections.