Assembly of Human Stratum Corneum Lipids In Vitro: Fluidity Matters

Lipid Monolayer on Cell Surface Protein Templates Functional Extracellular Lipid Assembly

“…Despite this solvent treatment, the CEs remained intact (Figure S2f,g, Supporting Information), confirming their resistance. The lipid films were annealed using an optimized protocol, [ 23 ] sandwiched in Franz diffusion cells, and examined for permeability (Figure 2c–f). Water loss values across CEs or sapCEs without free lipids were at their maxima, similar to solvent‐extracted or saponified SC.…”

“…[20][21][22] However, although isolated human SC lipids in vitro are able to assemble into a proper lamellar structure, LPP, they require additional fluidization to reduce nanoscopic packing defects and permeability. [23] We hypothesized that the corneocyte lipid envelope, CLE (Figure 1c), a lipid monolayer coating the corneocyte surface, [1,24] may template and locally fluidize the extracellular lipids. This lipid coat, rich in ultralong 𝜔-O-acylceramides, is covalently anchored to a highly cross-linked protein envelope on the cell surface, together forming the corneocyte envelope (CE).…”

“…[ 20–22 ] However, although isolated human SC lipids in vitro are able to assemble into a proper lamellar structure, LPP, they require additional fluidization to reduce nanoscopic packing defects and permeability. [ 23 ]…”

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

“…To study the robustness of the LPP and MLP arrangements, the lipid models with 20 mol% ω- O -acylCer/ω-OHCers were assembled at 90°C. The LPP was still present in the ω -O- acylCer model (similar to isolated human stratum corneum lipids ( 57 )), but in the ω-OHCer model, the MLP dissolved into the SPP and a 4.1 nm phase, rendering lipid films 3 and 8-fold more permeable.…”

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

“…The barrier lipids also share the extracellular space with enzymes, inhibitors, signaling molecules, and antimicrobial peptides, all of which would require less rigid, more dynamic environments for their action ( 68 ). Fluid chains are also needed during the barrier assembly to squeeze into and fill narrow extracellular spaces without significant packing defects and, hence, permeability ( 69 ). Here, we propose an LPP model of alternating rigid (FFA and Cer acyl chains) and dynamic layers (sphingosine-rich layer and isotropic linoleate slab; Fig.…”