(181ae) On the Self-Assembly of Skin Lipids Using Coarse-Grained Molecular Dynamics Simulation

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 that allow self-assembly to be studied on time scales accessible to molecular dynamics simulation. In particular, we will present results for mixed lipid systems involving ceramides 2 and 3, fatty acids and cholesterol. The accuracy of the coarse-grained models is validated by comparing the self-assembled structures against those obtained from simulations of pre-assembled atomistic lipid bilayers and experimental work where possible.  The effect of changing the cholesterol content of the lipid systems and unsaturation in lipid tails on the self-assembly process will be discussed.