Predicting Skin Interactions and Permeation of Chemical Agents using Computational Modelling

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The skin is the outermost barrier for most of the human body. The majority of chemicals that come into contact with the body will initially do so through an interaction with the skin. It is imperative, therefore, that a detailed understanding of the interaction of chemical agents with the skin is obtained to inform and improve processes such as the removal of chemical agents from the skin. Furthermore, chemical agents that enter the body frequently do so through permeating this skin barrier. Understanding and predicting this permeation is vital in both trying to prevent this permeation from happening, and in the assessment of previously uncharacterised hazardous chemical agents. This PhD project will develop and validate a novel and unique computational model of the stratum corneum membrane. The stratum corneum is both the outermost layer of the skin and the main barrier to skin permeation. This makes it ideal to study for both skin interactions and permeation. The studentship will involve extending the coarse-grained ELBA lipid model to include the lipids of the stratum corneum membrane. The ELBA model is unique in that it incorporates realistic electrostatic interactions (charges and dipoles) within a coarse-grained lipid model, and also allows hybrid atomistic/coarse-grained simulations to be performed. With the application of this model we aim to overcome the limitations associated with previous studies of the stratum corneum. The ultimate aim of the project will be to provide a predictive computational model regarding the interaction and permeation of chemical agents with the skin barrier.