(606e) Development and Self-Assembly of Coarse-Grained Skin Lipid Models Derived Via Multistate Iterative Boltzmann Inversion | AIChE

(606e) Development and Self-Assembly of Coarse-Grained Skin Lipid Models Derived Via Multistate Iterative Boltzmann Inversion


Moore, T. C. - Presenter, Vanderbilt University
Iacovella, C. R., Vanderbilt University
Hartkamp, R., Vanderbilt University
McCabe, C., Vanderbilt University
The barrier function of the skin is known to be localized to its outermost layer, the stratum corneum (SC). Specifically, the multilamellar lipid matrix surrounding the dead, flat corneocytes in the SC is thought to be the main barrier to chemical penetration through the skin. Although the chemical makeup of the SC is known, the molecular level details of its structure are not, with several different models proposed for the arrangement of this complex lipid mixture. Molecular simulation presents a suitable means to study such systems, allowing a clear molecular level perspective of the ordering and precise control over system composition. However, to date, simulations of SC lipids have focused primarily on preassembled structures. While such studies have offered much insight into lipid-lipid and lipid-water interactions, it is likely that the preassembled structures are unduly influenced by their initial configuration, due to the low diffusivity of the lipids. As such, self-assembled structures may present a more realistic view of SC lipid systems, although the long time scales needed due to the rough free energy landscape make atomistic level modeling impractical, necessitating the use of more computationally efficient coarse-grained models.
 Here we develop coarse-grained (CG) models and investigate the behavior of the key lipid classes present in human SC, namely ceramide (CER), cholesterol (CHOL), and free fatty acids (FFA). CG potentials are derived from atomistic simulations via multistate iterative Boltzmann inversion [1], which yields potentials with increased levels of transferability between states and thus are suited to study self-assembly. Particular emphasis is placed on the hydrophobic interactions, where wetting properties are used to tune the relative attraction between CG beads in order to accurately capture phase segregation at the CG level. We investigate the behavior of CER-rich bilayers and multilayers and find that the CG CERs self-assemble into assemblies that closely match several key structural properties of atomistic models and experimental CER systems.[3] Self-assembly of mixed lipid systems is then investigated to probe structural conformations of more realistic SC mixtures and explore the relevance of several experimentally proposed models of SC lamellar organization.


[1] Moore, T. C., Iacovella, C. R. & McCabe, C. Derivation of coarse-grained potentials via multistate iterative Boltzmann inversion. J. Chem. Phys. 140, (2014).

[2] Bouwstra, J. A., Gooris, G. & Ponec, M. The lipid organisation of the skin barrier: Liquid and crystalline domains coexist in lamellar phases. J. Biol. Phys. 28, 211â??223 (2002).

[3] Moore, T. C., Iacovella, C. R., Hartkamp, R. & McCabe, C. A Coarse-grained Model of Stratum Corneum Lipids: Free Fatty Acids And Ceramide NS. Submitted.