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 to with phospholipid bilayers. The average time it takes for a water molecule to cross the bilayer is calculated by solving the Smoluchowski equation in 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 τ av = 0.69 ms. The permeability is about 30 times smaller than existing experimental results on mammalian skin sections.

Interaction of menthol with mixed-lipid bilayer of stratum corneum: A coarse-grained simulation study

“…Given the complexity of the composition of the skin lipids and the consensus over their molecular architecture, many researchers have developed skin-lipid 'substitutes' to explore the interaction of molecules within SC using MD simulation, which has a barrier function simi- lar to skin tissue [32]. Both single-component models [33][34][35][36] and mixed skin-lipid models with different compositions and contents [37][38][39][40] have been investigated. Das et al demonstrated that the simulated model bilayers comprising of CER2 (ceramide NS, the predominant ceramide in skin lipid with a C24:0 fatty acid tail, short for CER in the following passage), FFA (C24:0) and CHOL at ratio close to 2:2:1 has the most desirable properties of good barrier function and stability against mechanical stress [38,39].…”

“…Both single-component models [33][34][35][36] and mixed skin-lipid models with different compositions and contents [37][38][39][40] have been investigated. Das et al demonstrated that the simulated model bilayers comprising of CER2 (ceramide NS, the predominant ceramide in skin lipid with a C24:0 fatty acid tail, short for CER in the following passage), FFA (C24:0) and CHOL at ratio close to 2:2:1 has the most desirable properties of good barrier function and stability against mechanical stress [38,39]. Therefore, it can be used to investigate the interactions and elucidate the molecular mechanisms of the penetration enhancement effect of menthol.…”

Recent development in computer simulations of lipid bilayers

“…Studies of the gel to liquid-crystal phase transitions of fully hydrated bilayers were also performed 147,149,150 . It should be mentioned also a series of MD simulations of the specific branch-chained lipid bilayers [151][152][153][154][155] and a ceramide bilayer [156][157][158] .…”

“…Water permeability for a bilayer composed of a 2:2:1 molar ratio of ceramide NS 24:0 (ceramide 2) -CHOL -free FA 24:0 was estimated with extended ensemble MD in 158 .…”

The physics of stratum corneum lipid membranes

“…A series of simulations with a single water molecule constrained to remain at a fixed distance z from the midplane was used to calculate the local (in z) excess chemical potential and diffusivity of water inside SC lipid bilayers [26]. A large barrier for penetration (approx.…”