Coarse-Grained Simulations of the Self-Assembly of Skin-Relevant Lipid Structures

The barrier properties of the skin are largely governed by the lipid lamellae of the outermost layer of skin, the stratum corneum (SC). While the composition of the SC is known, the molecular-level features of the lipid organization are not. This information would be useful for repairing an impaired skin barrier or selectively bypassing the barrier, e.g., for transdermal drug delivery. Molecular simulation allows precise control over system composition and direct visualization of the system structure, making it a useful tool for studying such systems. The slow kinetics of lamellar self-assembly make using atomistic models computationally inefficient. Thus, coarse-grained models, where groups of atoms are treated as individual interaction sites, are employed to study the self-assembly of SC lipids. Here, coarse-grained models of SC lipids, including CER NS C16, CER NS C24, cholesterol, and free fatty acids, are simulated to gain insight into the low-energy structures adopted by mixtures of these lipids. Self-assembly of both single and stacked bilayers in solution is studied by cooling systems from a high-temperature, disordered state. Structural properties, such as lipid positioning, angle between lipid tails, tilt angle of lipid tails, nematic order parameter, and bilayer lipid density are calculated. These properties are compared between simulations to determine the effects of lipid concentration on bilayer structure. This research increases understanding of the structural role of various lipids in SC organization and is an important step in the use of accurate coarse-grained models of the SC lipids.