(717c) The Influence of Lipid Tail Length and Cholesterol Content on the Structure of Model Stratum Corneum Bilayers

The skinâ??s ability to act as a barrier between the internal and external environments of the body is controlled by the stratum corneum (SC), the thin outermost layer of the epidermis. The SC is composed of corneocytes, surrounded by a dense lamellar lipid matrix composed of ceramides (CER), cholesterol (CHOL), and free fatty acids. Skin disease is often coincident with an altered SC lipid composition and a decreased barrier function, e.g., elevated levels of CHOL [1] have been observed for lamellar ichthyosis patients and increased level of short-chain CER [2] for atopic eczema patients. Although a connection between SC lipid composition and skin barrier function is clear, the mechanism is not clearly understood, due to the fact that composition may vary between samples and molecular arrangements must be inferred from spectroscopic experiments. Molecular simulation offers a promising complement to experimental work, as it allows precise control over system composition and atomic-level resolution. However, the dense gel and crystalline phases formed by the SC lipids substantially limits molecular mobility at physiologically relevant conditions, and thus molecular simulations may fail to reach equilibrium and the results may be unduly influenced by the initial starting morphology of the lipids.

Here, we investigate the structural dependence of SC model lipid bilayers on CER tail length and CHOL content using a modified version of simulated tempering [3]. Simulated tempering, whereby a simulation undergoes a random walk through temperature space, provides a means for systems to escape energetic traps and explore phase space, allowing the system to efficiently decorrelate from the initial, assumed configuration. To investigate the role of the CER tail length on bilayer structure, a series of systems are studied in which the relative amount of short and long-chain CER is varied. Similarly, systems with varying amounts of CHOL are studied to probe the role of CHOL content on bilayer structure. We find that several key structural properties are dependent on both CER tail length and CHOL content, including a strong dependence of tilt angle and interdigitation behavior on the relative lipid concentration, both of which may have significant implications for the barrier function. These results provide new insights into the connections between lipid composition, structure, and barrier properties of the SC.

References

[1] Lavrijsen, A. P. M. et al. Reduced Skin Barrier Function Parallels Abnormal Stratum Corneum Lipid Organization in Patients with Lamellar Ichthyosis. J. Invest. Dermatol. 105, 619â??624 (1995).

[2] Janssens, M. et al. Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J. Lipid Res. 53, 2755â??2766 (2012).

[3] Marinari, E and Parisi G. Simulated Tempering: a New Monte Carlo Scheme. Europhys. Lett. 19 (6), 451-458, (1992)