Molecular Dynamics Simulation of Skin Lipids: Effect of Ceramide Chain Lengths on Bilayer Properties

Abstract

Stratum corneum (SC), the outer layer of skin, serves as a barrier for pathogens and maintains the trans-epidermal water loss. The lipid matrix of SC is the major diffusion-rate-limiting pathway as molecules will have to pass through it. Ceramides play a key role in structuring and maintaining the barrier function of the skin. In this study, atomistic molecular dynamics (MD) simulations were used to systematically investigate the effects of the chain length of ceramide (CER) tails on the properties of the bilayer at a skin temperature of 310 K. The barrier properties were examined by means of permeation studies of water through the model membrane using steered MD simulations. Our studies revealed that shorter chains of one leaflet of the bilayer do not interdigitate with the chains of the other leaflet and lead to more free space in the middle of the bilayer, thereby leading to higher permeability. In CERs with dissimilar chain lengths, the lipids on one chain interdigitate with the other leaflet lipids, increasing the electron density in the middle of the bilayer. The bilayer thickness increases with increase in the CER chain length. The permeability of smaller-chain CERs was found to be an order of magnitude higher than that of the longer-chain CERs.

Effect of Size and Surface Charge of Gold Nanoparticles on their Skin Permeability: A Molecular Dynamics Study

“…The free energy profile shows no barrier in the interior of the bilayer for neutral hydrophobic AuNPs so diffusion controlled the permeability. Similar phenomena has also been reported earlier for hydrophobic nanoparticle and hydrophobic molecules permeation through bilayer2954. The free energy for each AuNP in the interior of the bilayer was negative (energetically favorable) but the diffusion coefficients decreased significantly with increasing size.…”

“…The independency of diffusion to permeate size, in the bilayer interior, as compared to the water, was previously reported57, and relatively constant values along with the bilayer normal were previously reported for a nifedipine drug analog58. However, the diffusion constant values of the small molecular permeates changed with respect to z, and it has been correlated to membrane heterogeneity (differences in free volume)545557. The diffusion values were found to be higher for smaller AuNP as compared to larger nanoparticles.…”

“…The reason could be that the DPPC bilayer used in earlier studies4448505152 was at above the gel to liquid phase transition temperature while in our simulation the skin lipid bilayer was in gel phase. The free energy of permeation of water through gel phase pure ceramide skin layer5354 (~ 47.6 kJ/mol) and liquid phase DPPC bilayer55 (~22.9–26 kJ/mol) has been reported earlier. Li et al 56.…”

Age- and Diabetes-Related Changes in the Free Fatty Acid Composition of the Human Stratum Corneum

“…Additionally, ceramides (CERs) are synthesised in the endoplasmic reticulum of the keratinocytes, and their anisometric molecular structure differs markedly from other lipid classes [15,16]. Due to load differences within their long-chain molecules, CERs are able to spontaneously form lyotropic mesophases (also known as liquid-crystalline membrane structures) [17,18]. Unlike phospholipids, functionally important CERs in the SC contain 2 alkyl chains of different lengths.…”

Perspective: Computational modeling of accurate cellular membranes with molecular resolution

“…Efforts have been made to study the biophysical properties of key lipid components with a single bilayer for the CHARMM36 and GROMOS force fields. 52,[110][111][112][113][114][115][116][117][118][119][120] Many have focused on using three-lipid models of a ceramide, fatty acid, and cholesterol to mimic the SC. Moore et al 110 found that bilayer thickness depends strongly on the level of tail-length asymmetry and permeability strongly depends on tail-length variation.…”