(244h) Simulation Study of Stratum Corneum Lipid Self-Assembly

The outermost layer of the skin, the stratum corneum (SC), is primarily responsible for preventing water from leaving and external chemical agents from entering the body. The SC is composed of corneocytes surrounded by a dense extracellular lipid matrix, to which the barrier function of the skin is localized for many chemicals. The lipid matrix is composed of cholesterol and several types of ceramides and free fatty acids of varying length. X-ray scattering experiments reveal that the lipid matrix in healthy skin organizes into two coexisting lamellar phases: a 6 nm short periodicity phase (SPP) and a 13 nm long periodicity phase (LPP).¹ Experimental studies of isolated SC lipids found that the LPP only forms in the presence of ceramides with a very long chain (~50 carbons) with CER EOS being the most common in human skin. Skin diseases that weaken the SC barrier properties, such as atopic dermatitis, have been linked to a lower concentration of CER EOS and a decreased presence of the LPP compared to healthy skin, suggesting that the LPP plays an important role in skin barrier function. Lipid arrangements in the LPP are largely unknown. Here we use coarse-grained molecular dynamics simulations to gain a better understanding of the LPP structure and arrangement. Specifically, we examine a simple, four-component, SC lipid mixture comprised of CER EOS and one other ceramide, cholesterol, and lignoceric acid known experimentally to form the LPP.² We investigate the self-assembly of these lipids into lamellar structures starting from randomized initial configurations and compare to experimental neutron and X-ray scattering of the LPP.²

References

[1] J. A. Bouwstra, G. S. Gooris, J. A. van der Spek, W. Bras, “Structural investigations of human stratum corneum by small-angle X-ray scattering,” J. Invest. Dermatol., 1991, 97, 1005-1012.

[2] C. M. Beddoes, G. S. Gooris, F. Foglia, D. Ahmadi, D. J. Barlow, M. J. Lawrence, B. Demé, J. A. Bouwstra, “Arrangement of Ceramides in the Skin: Sphingosine Chains Localize at a Single Position in Stratum Corneum Lipid Matrix Models,” Langmuir, 2020, 36, 10270-10278.