The human body’s first line of defense against pathogens is provided by the outermost layer of the skin, the stratum corneum. The lipids in this layer are chemically distinct from those in the plasma membrane of viable cells, and form a multi-lamellar matrix with unique characteristics. When the chemical makeup of the skin's lipids is perturbed, or after a very long exposure to water, the permeability of the skin increases dramatically. This is consistent with the formation of many nanometer-wide water channels, as proposed previously in studies based on measured skin permeabilities. Key to the formation of these channels is the presence of water already embedded in the outer skin.

The cover image for the April 7 issue of Biophysical Journal is a rendering of a simulation snapshot that shows the organization of excess water in the skin's lipids. Molecular-dynamics simulations were based on a model lipid composition that has been shown to effectively describe the skin's lipid matrix. Instead of spreading uniformly and allowing the lipid lamellae to separate, excess water aggregates into the lamellae, as droplets a few nanometers in diameter. These droplets contain a rather small amount of water, and may remain embedded for long times. An experimentally based structural model shows that coalescence of the droplets into channels is promoted by changes in the amount of water or in the mechanical properties of the surrounding lipids.

In most images of molecular systems in biophysics, water is the most abundant substance and is generally hidden to highlight the organization of proteins and lipids. This figure shows an example where water is very scarce, and for this reason, the lipids are hidden instead in order to highlight the water's structure. The non-homogeneous density of the droplets of three skin lipid lamellae is shown. Despite being evenly distributed along each lipid lamella, the droplets themselves do not feature a well-defined shape or a periodic lattice, making it more difficult for X-ray or neutron beams to resolve the droplets individually.

As in other biological tissues, the equilibrium between different physical states is one of the methods by which a specific function is fulfilled. For mammalian skin, an increased control over these states will allow understanding of how healthy and unhealthy skin work differently, as well as improving how drugs are delivered through the skin without a needle.

- Christopher MacDermaid, Kyle Hall, Russell DeVane, Michael Klein, Giacomo Fiorin