ω-O-Acylceramides but not ω-hydroxy ceramides are required for healthy lamellar phase architecture of skin barrier lipids

The intriguing molecular dynamics of Cer[EOS] in rigid skin barrier lipid layers requires improvement of the model

“…The localization of the isotropic linoleates in a layer-like fashion between the rigid acyl chains is consistent with the thin electron-dense band in transmission electron microscopy with RuO 4 staining in both mature SC lipids and, importantly, in the precursor lipid lamellae in lamellar bodies ( 3 ). In mice with deficient-PNPLA1, a transacylase required for the linoleate attachment to form Cer[EOS], this band is absent ( 71 ). The isotropic linoleate slab in the hydrophobic core of both precursor and mature lipid lamellae resembles a lipid droplet lens ( 72 ), which makes sense as lipid droplet triglycerides are a source of linoleate for Cer[EOS] synthesis ( 73 ).…”

Lipid Biomimetic Models as Simple Yet Complex Tools to Predict Skin Permeation and Drug–Membrane Biophysical Interactions

“…In studies comparing three different methods for lipid airbrushing—manual, using a rotor, or the Linomat—the Linomat apparatus was found to be the most suitable for preparing SCS due to its efficiency and the uniformity of the membrane thickness compared to the other two methods. Although using benzoic acid as model compound, the steady-state flux was similar for the three SCS, and the values were very similar to human SC, so the authors selected the Linomat as the most appropriate apparatus for preparing the SCS [ 185 ]. Furthermore, the most critical factors in the spraying protocol to ensure the suitability of the SCS for permeability tests, in which it is imperative to obtain a densely packed and uniform layer, were investigated [ 58 ].…”

Current insights into skin lipids and their roles in cutaneous health and disease

“…The use of molecular simulation is an efficient system to study the complexity of stratum corneum lipids and understand the physicochemical properties, organization and configurations necessary for correct barrier function [60 ▪▪ ]. Recent insights based on in-silico model studies include a detailed understanding of the orientation of the ceramide headgroups and localization of phytosphingosine ceramides in model membranes [61 ▪▪ ,62], requirement of ω-O-acylceramides for the correct architecture of lamellar phase in barrier lipids [63 ▪▪ ], and the effect of cholesterol composition on stratum corneum lipid organization [64]. Finally, recent advances in high-resolution cryo-electron microscopy allowed for elucidation of the structure of the skin's barrier and its formation, providing further understanding of the role of stratum corneum lipids [65 ▪ ].…”