Simulations of Pure Ceramide and Ternary Lipid Mixtures as Simple InteriorStratum CorneumModels

Abstract

The barrier function of the stratum corneum (SC) is intimately related to the structure of the lipid matrix, which is composed of ceramides (Cer), cholesterol (Chol), and free fatty acid (FFA). In this study, the all-atom CHARMM36 (C36) force field is used to simulate bilayers of N-palmitoylsphingosine (Cer16), N-lignoceroylsphingosine (Cer24), Chol, and lignoceric acid (LA) as simple models of the SC. Equimolar mixtures of Cer, Chol, and LA are replicated from experiment for comparison and validation of the C36 force field, and the effects of lipid diversity and temperature are studied. The presence of Chol and LA have effects on nearly all membrane properties including surface area per lipid, area compressibility moduli, chain order, Chol tilt, bilayer thickness, interdigitation, hydrogen bonding, and lipid clustering, while temperature has a more moderate effect. In systems containing Cer16, there is a profound difference in interdigitation between pure Cer and mixed systems, while systems containing Cer24 are relatively unaffected. Increasing temperature has the potential to shift hydrogen bonding pairs rather than uniformly decrease bonding, which can lead to greater Cer-Cer bonding at higher temperatures. Comparison with deuterium order parameter experiments demonstrates good agreement, which supports further use of this class of lipids and fatty acids for development of more complex SC models.

Insight Into the Molecular Dynamic Simulation Studies of Reactive Oxygen Species in Native Skin Membrane

“…The APL of native skin-lipid bilayer is shown in Supplementary Figure S1 . The calculated APL was 0.32 ± 0.003 nm, which was comparable to that reported in previous studies (0.31 nm) ( Gupta and Rai, 2015 ) and (0.33 ± 0.01 nm) ( Wang and Klauda, 2018 ). Similarly, the thickness of the native skin-lipid bilayer membrane was calculated on the last 50 ns of simulation and was found to be 4.98 nm, which was comparable to those reported in previous experiments (5.12 nm) ( Gupta and Rai, 2015 ) and (5.17 nm) ( Das et al, 2009 ).…”

Molecular mechanism of the skin permeation enhancing effect of ethanol: a molecular dynamics study

“…Earlier studies have shown signicant effects of CER type and FFA chain length on skin permeation properties. [51][52][53][54][55][56]58 As seen in simulations, ethanol interacts with headgroup atoms of skin lipids and makes hydrogen bonds with them, i.e., it reduces hydrogen bonding capabilities of lipid headgroup with each other and reduces the barrier function of skin SC. The skin SC possesses various types of ceramides and ethanol interacts with each one very differently due to their headgroup structure (number and position of -OH groups).…”

Computational Modeling of Realistic Cell Membranes

“…656−659 Wang and Klauda characterized bilayer properties of pure ceramide bilayers and SC ternary models using the CHARMM FF at different temperatures and ceramide tail length. 660 Höltje et al modeled the SC with a combination of fatty acids and cholesterol using the GROMOS FF. 661 Das et al constructed a SC model containing 15 ceramide variants as well as a fatty acid and cholesterol using the atomistic Berger lipid FF and found a preference for the inverse micellar phase.…”