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 the lipid structure of intact SC can be reproduced experimentally with model systems using synthetic lipids,1 the organization and role of each lipid in determining 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 However, such simulations can suffer from initialization bias due to low lipid mobility. Furthermore, 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 The self-assembly of mixtures of CERs, CHOL, and FFAs are studied into multilayer assemblies. Atomistic configurations are then generated by back-mapping the self-assembled multilayer CG configurations and in turn provide new insight into SC lipid organization and structure.
References
[1] J. A. Bouwstra and M. Ponec, “The Skin Barrier in Healthy and Diseased State,” Biochimica et Biophysica Acta – Biomembranes, 1758, 2080-2095 (2006).
[2] P. Shamaprasad, C. O Frame, T. C. Moore, A. Yang, C. R. Iacovella, J. A. Bouwstra, A. L. Bunge and Clare McCabe, “Using Molecular Simulation to Understand the Skin Barrier” Progress in Lipid Research, 88, 101184 (2022).
[3] T.C. Moore, C. R. Iacovella, and Clare McCabe, “Derivation of Coarse-Grained Potentials via Multistate Iterative Boltzmann Inversion,” J. Chem. Phys, 140(22) 224104 (2014).
References
[1] J. A. Bouwstra and M. Ponec, “The Skin Barrier in Healthy and Diseased State,” Biochimica et Biophysica Acta – Biomembranes, 1758, 2080-2095 (2006).
[2] P. Shamaprasad, C. O Frame, T. C. Moore, A. Yang, C. R. Iacovella, J. A. Bouwstra, A. L. Bunge and Clare McCabe, “Using Molecular Simulation to Understand the Skin Barrier” Progress in Lipid Research, 88, 101184 (2022).
[3] T.C. Moore, C. R. Iacovella, and Clare McCabe, “Derivation of Coarse-Grained Potentials via Multistate Iterative Boltzmann Inversion,” J. Chem. Phys, 140(22) 224104 (2014).
