(691e) Multiscale Modeling of Stratum Corneum Lipids

The barrier function of the human skin is primarily located in the stratum corneum (SC), which is composed of corneocytes surrounded by a dense, lamellar lipid matrix made up of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs) of various lengths. While experimentalists can reproduce the lipid organization of intact SC with model systems using synthetic lipids,¹ the role of each lipid in determining the molecular structure of the SC, and hence the barrier properties of skin, is not well understood due to the complex nature of the SC lipid matrix. To address this need, atomistic molecular dynamics (MD) simulations of pre-assembled lipids in primarily bilayer configurations have been used to study the behavior of the SC lipids.^2,3 However, such simulations can suffer from initialization bias due to low lipid mobility, and further, simple bilayers are not representative of the complex multilayer structure of the SC. In order to access the long timescales and large system sizes needed to self-assemble multilamellar structures, we have developed computationally efficient coarse-grained (CG) models using the Multi-State Iterative Boltzmann Inversion (MS-IBI) method² based on simulation data from fully atomistic models for commonly studied SC lipids: CER NS, NP, AP, AS, FFA, and CHOL.³ We study the self-assembly of large complex multilayer mixtures of multiple CERs, CHOL, and FFAs that match previously examined experimental compositions. Atomistic configurations generated by back-mapping the self-assembled multi-lamellar CG configurations provide insights into lipid organization and structure of more realistic SC lipid systems than are currently available and are used to examine hypotheses generated from experimental observations from neutron scattering.

References

[1] J. A. Bouwstra and M. Ponec, “The Skin Barrier in Healthy and Diseased State,” Biochimica et Biophysica Acta - Biomembranes. 2006, vol. 1758, pp. 2080-2095.

[2] T.C. Moore, C. R. Iacovella, and Clare McCabe, “Derivation of Coarse-Grained Potentials via Multistate Iterative Boltzmann Inversion,” J. Chem. Phys, 2014, vol. 140, no. 22, p. 224104.

[3] T. C. Moore, C. R. Iacovella, R. Hartkamp, A. L. Bunge, and C. McCabe, “A Coarse-Grained Model of Stratum Corneum Lipids: Free Fatty Acids and Ceramide NS,” J. Phys. Chem. B, 2016, vol. 120, no. 37, pp. 9944–9958.