Simulation Study of the Long-Periodicity Phase of the Stratum Corneum

The stratum corneum (SC), which is the outermost layer of the skin, plays an important role in preventing water loss from the body and protecting against external chemical penetrants. The SC is comprised of corneocyte cells surrounded by an extracellular lipid matrix that is primarily responsible for barrier function. The lipid matrix follows a lamellar organization and consists of several types of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFA) with varying tail lengths. X-ray scattering experiments have revealed that a 6 nm short-periodicity phase (SPP) and a 13 nm long-periodicity phase (LPP) coexist in the lipid matrix of healthy skin. [1] Furthermore, studies of model experimental lipid mixtures found that the LPP only forms in the presence of very long ceramides (CER-EOS). A decreased presence of the LPP phase as well as deficiencies in CER-EOS is observed in SC lipid samples from atopic dermatitis patients, which exhibit weaker barrier properties compared to healthy SC. As such, the LPP is believed to be a crucial component of the skin barrier. Here we use molecular dynamics simulations to better understand the structure and arrangement of lipids in the LPP. In particular, we examine mixtures of ceramides including CER-EOS, CHOL, and FFA, which are known to form only the LPP. [2]

[1] J. A. Bouwstra, G. S. Gooris, J. A. van der Spek, W. Bras, "Simulation study of the long-periodicity phase of the stratum corneum", J. Invest. Dermatol., vol. 97, no. 6, pp. 1005-1012, 1991

[2] C. M. Beddoes, G. S. Gooris, and J. A. Bouwstra, “Preferential arrangement of lipids in the long-periodicity phase of a stratum corneum matrix model,” J. Lipid Res., vol. 59, no. 12, pp. 2329–2338, Dec. 2018.