Effect of monoglycerides and fatty acids on a ceramide bilayer

Abstract

Monoglycerides and unsaturated fatty acids, naturally present in trace amounts in the stratum corneum (top layer of skin) lipid matrix, are commonly used in pharmaceutical, cosmetic and health care formulations. However, a detailed molecular understanding of how the oil additives get incorporated into the skin lipids from topical application and, once incorporated, how they affect the properties and integrity of the lipid matrix remains unexplored. Using ceramide 2 bilayers as skin lipid surrogates, we use a series of molecular dynamics simulations with six different natural oil ingredients at multiple concentrations to investigate the effect of the oils on the properties and stability of the bilayers. The six oils: monoolein, monostearin, monoelaidin, oleic acid, stearic acid and linoleic acid - all having the same length of the alkyl chain, C18, but a varying degree of saturation, allow us to systematically address the effect of unsaturation in the additives. Our results show that at low oil concentration (∼5%) the mixed bilayers containing any of the oils and ceramide 2 (CER2) become more rigid than pure CER2 bilayers due to more efficient lipid packing. Better packing also results in the formation of larger numbers of hydrogen bonds between the lipids, which occurs at the expense of the hydrogen bonds between lipids and water. The mixed bilayers with saturated or trans-unsaturated oils remain stable over the whole range of oil concentration. In contrast, the presence of the oils with at least one cis-double bond leads to bilayer instability and complete loss of bilayer structure at the oil content of about 50-65%. Two cis-double bonds in the lipid tail induce bilayer disruption at even lower concentration (∼30%). The mixed bilayers remain in the gel phase (without melting to a fluid phase) until the phase transition to a non-bilayer phase occurs. We also demonstrate that the stability of the bilayer strongly correlates with the order parameter of the lipid tails.

Mechanisms of lipid extraction from skin lipid bilayers by sebum triglycerides

“…The retention in the bilayer and the adsorption is facilitated by the strong hydrogen-bond network formed by the Bulk-TG 3.3 CHO flip-flop and FFA escape CR2 head groups. This network has been previously observed and discussed in several simulation studies 22,33,38,39 and in the ESI (see section S5.3). A higher fraction of CR2 lipids (≈ 11%) partially detach from the bilayer, with one of the aliphatic chains remaining within the bilayer while the other moves to the sebum, resulting in an angle of ≈ 180 • between the two chains (see blue box in Fig.…”

“…In addition, more complex mixtures consisting of ceramides, cholesterol and free fatty acids have been investigated to assess the impact of the lipid composition on the permeability, structure and fluidity of the SC membrane 18,[27][28][29][30][31] . The permeation of small molecules 19 , ethanol 19,32 , DMSO 19,22 , oils 33,34 and nanoparticles 35,36 has also been quantified using MD simulations 2 . Most simulations on skin lipids have focused so far on bilayers or stacks of bilayers in contact with water.…”

DL_MONTE: a multipurpose code for Monte Carlo simulation

“…see [74]. Note that S z can be linked to the deuterium parameter and is estimated to be normally twice the latter [76]. The overall z-order for bonded carbon-based triplets (see below) is also reported in [70] for POPC CG lipids modelled with the Dry Martini force-field, S z,POPC = 0.35.…”

Permeation pathways through lateral domains in model membranes of skin lipids

“…This was followed by simulations of more complex mixtures of ceramides, CHOL and free fatty acids, which revealed how the ratio between different lipid classes contributes to the properties of the SC and explored the relationship between the polydispersity of the lipids and the overall packing and fluidity of the resultant membrane [36][37][38][39][40][41][42] . Additional simulation studies have explored the effect of additives such as ethanol 43 , DMSO 32,44 and oils 45,46 and have attempted to characterize the permeation of small molecules through homogeneous skin-lipid membranes 37,43,47 . In this work we characterize model membranes of CER[NS]24, CHOL and FFA24 at different levels of hydration and explore the lateral and perpendicular pathways of water across the membranes using atomistic MD simulations and potential of mean constraint force calculations.…”