(775d) On the Development of Coarse-Grained Models for Skin Lipids

It has been shown that the skin’s ability to act as a barrier to harmful agents entering the human body and to reduce water loss from the body is related to the structure of the lipids between the corneocytes in the outmost layer of skin, also known as the stratum corneum (SC). To obtain a molecular-level understanding of how the SC lipids (namely ceramides, cholesterol and free fatty acids) self-assemble into bilayers, and other structures, we have developed coarse-grained models for these lipids. Due to the time scale required to observe self-assembly in such systems, detailed atomistic simulations cannot be utilized. Consequently, coarse-grained (CG) models, which reduce the atomistic detail in the representation of a molecule and allow the simulation or larger spatial and temporal scales, are needed. In this work, of the 9 ceramides found in human skin, we focus on cermides 2 and 3 and using the iterative method formulated by Reith, Pütz, and Müller-Plathe, have developed center-of-mass based coarse-grained models for use in molecular dynamics simulations. Results of the self-assembly simulations will be reported the accuracy of the coarse-grained models validated by comparing the self-assembled structures against those obtained from pre-assembled lipid bilayers previously investigated at the atomistic level. Additionally the heuristics of performing coarse-grained self-assembly simulations of ceramide lipids with respect to the effects of different initial configurations and hydration levels will be discussed.