Advanced Computation


The skin is the largest organ of our body, protecting it from the direct impact of the external environment, preventing dehydration of the organism and limiting permeation of substances from the enviroment directly into the organism. However, many substances are known to permeate the skin. This characteristic of the skin is advantageous for local treatment using ointments and other transdermal applications. On the other hand, we have to protect our skin from permeation by some types of undesirable substances (for instance, herbicides, fungicides, organic solvents such as alcohols or petrol and many other toxic compounds). This is why new substances present in cosmetics, detergents and cleaning products which come into contact with skin have to be tested for their permeability through the skin and how they will impact upon the skin’s permeability as a whole. Because experiments testing the permeation of substances are neither trivial nor cheap and require a source of human skin, the method by which the interaction and permeability of substances through the skin can be described effectivelly is computational chemistry.

RCPTM has realised this research, thanks to significant support from Procter & Gamble Company. Computer simulations are used to model the permeability of various commercially significant substances through the top protective layer of the skin (the so called stratum corneum). Currently, simplified models of the lipid bilayer are studied. Computer simulations allow to determine how substances accumulate in the lipid bilayer and how easily they are able to pass through it. RCPTM works on the development of stratum corneum model at the same time, but this task is complicated by the fact that it is a highly comlex structure created by ceramides, free fatty acids and cholesterol.

A simple model of the interaction between the membrane (colourful spheres represent lipid polar heads, light blue chains non-polar lipid chains and grey dots represent water) with a model caffeine molecule (the lighter molecule). The free caffeine energy profile (red line) allows us to determine how caffeine accumulates in the membrane (depending upon the depth of the profile) and where it may be found most frequently (at the deepest point of the free energy profile).

The simplest model stratum corneum – on the left a pure bilayer of ceramides (water molecules are depicted in grey, lipids in blue-grey, polar sections are blue spheres, yellow and orange spheres represent the position of the lipid chain ends) and on the right a mixture of ceramide, free fatty acid, and cholesterol. In both cases the gel phase is visible in which the ceramide chains are ordered in a very regular manner. This structure significantly limits the permeability of the ceramide layers.

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