A Molecular Dynamics Study of the Self-Assembly of Human Skin Lipids

Abstract

This thesis details the development and testing of coarse-grained models for the key lipids found in the outmost layer of human skin, the straum corneum. Specifically, the development and optimization of coarse-grained models for free fatty acids, cholesterol, and water that can be used in molecular dynamics simulations are presented. The results show that the degree of accuracy of the models with respect to retaining structural behavior and target properties in comparison to atomistic molecular dynamics simulations and experimental data is good. Unique to this work is the development of coarse-grained models that are capable of studying the crystalline-solid phases of the lipid molecules, which will be important in the study of the crystalline-like lipid bilayers seen in the skin. The coarse-grained potentials developed from simulations of pure lipids are found to be transferable to other lipids, and in most cases, to the study of mixed lipid systems. Additionally, in the development of the model for water, a new approach, the K-means algorithm, was used to map multiple water molecules to a single coarse-grained site. This enabled a multi-bead water model for use in coarse-grained simulations that is compatible with other center-of-mass based coarse-grained models to be proposed. In this work, a four-water bead was found to provide the right balance between computational efficiency and solvation properties. Finally, as a test of the coarse-grained models developed, the self-assembly of a mixed lipid system was studied in a molecular dynamics simulation. The bilayer structure formed was found to be in good agreement with experimental work and the simulations provide insight into the observed experimental behavior.