(581a) Understanding the Structural Arrangements of Stratum Corneum Lipids through Coarse-Grained and Fully Atomistic Molecular Dynamics Simulations

Authors: 
Moore, T. C., Vanderbilt University
Iacovella, C. 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 rich lipid matrix that surrounds 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 the complex lipid mixture.  In this regard, molecular simulation presents a useful means to study such systems, providing a clear molecular level perspective of the ordering. However, to date, simulations of SC lipids have focused primarily on preassembled structures containing a small number of different lipids. 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, and thus are not representative of the molecular structures present in the skin. As such, self-assembled structures may present a more realistic view of SC lipid systems, as the free energy landscape of these types of systems is likely rough, and observing a transition between different states may be highly unlikely in the timescales accessible to atomistic simulation.

     In this work, we present the results of molecular dynamics simulations using both atomistic and coarse-grained (CG) forcefields recently developed by our group.  The atomistic forcefield has been developed and validated within the CHARMM forcefield formalism1 and the CG model derived using the recently developed multi-state iterative Boltzmann inversion method.2 Specifically, CG models are used to capture the long timescales needed to observe self-assembly into bilayer/lamellar structures; these morphologies are then used to create preassembled configurations for atomistic models that should be more representative of low free energy structures found in SC lipid mixtures. These results provide a clear, robust understanding of the structural and morphological arrangement of lipids within the SC.

References

1. Guo, S.; Moore, T. C.; Iacovella, C. R.; Strickland, L. A.; McCabe, C. “Simulation study of the structure and phase behavior of ceramide bilayers and the role of lipid headgroup chemistry.” Journal of Chemical Theory and Computation 2013, 9, 5116–5126.

2. Moore, T. C.; Iacovella, C. R.; McCabe, C. “Derivation of coarse-grained potentials via multistate iterative Boltzmann inversion.” The Journal of Chemical Physics 2014, 140, 224104.