Preferential arrangement of lipids in the long-periodicity phase of a stratum corneum matrix model

Abstract

With the use of model systems, previous work has identified the relative positions of several of the lipid subclasses (17)(18)(19). CERs with a nonhydroxyl C24 acyl chain linked to a C18 sphingosine (NS) and FFAs were located in the central region of the LPP trilayer structure, while CHOL remained exclusively in the outer region (18). CER EOS is uniquely positioned in both the outer and interior regions, with the head groups present at the boundary of the unit cell, while the carbon chain extends to the central head Abstract The lipid matrix of the stratum corneum, the outermost skin layer, consists primarily of ceramides, cholesterol, and FFAs. These lipids form a trilayer long-periodicity phase (LPP) that is unique to this barrier. Knowledge about the LPP is essential in understanding the barrier function. Previous studies of LPP lipid models have identified the position of the major lipid classes and suggested that a large fraction of FFAs and the ceramide acyl chain are present in the central region. However, the precise arrangement, such as lipid subclass mixing (isolated or mixed) and ceramide conformation (extended or hairpin), remains unknown. Here, we deuterated FFAs and the ceramide acyl chain to study CD 2 and CH 2 interactions with Fourier-transform infrared spectroscopy. The ceramide and FFAs of various chain lengths were not in separate domains but had mixed together. The larger number of CD 2 -CD 2 lipid chain interactions in the LPP than in a symmetrical bilayer structure implied that the ceramide had primarily adopted an extended conformation. Shorter FFAs were present in the central region of the LPP. This model explores the biophysical properties of the stratum corneum's LPP to improve the understanding of the barrier function of this layer.-Beddoes, C. M., G. S. Gooris, and J. A. Bouwstra. Preferential arrangement of lipids in the long-periodicity phase of a stratum corneum matrix model.

Coexistence of lipid phases stabilizes interstitial water in the outer layer of mammalian skin

“…Because self-assembly simulations of skin lipids cannot be carried out at atomistic detail, it is difficult to attribute these two discrepancies to the CG force field. Recent atomistic simulations (Wang & Klauda, in press) initialized with the "sandwich" LPP model (Beddoes et al, 2018;Bouwstra et al, 2001;Mojumdar et al, 2015a) show that this model is meta-stable on the µs time scale at 5:1 water:lipid, but unstable at 2:1 water:lipid. It is unclear if this result is due to experimental uncertainty in the water content, or the inability of simulation models to sustain a dehydrated phase of the skin lipids.…”

“…Permeation across such interface yields accurate predictions of the permeability of lipophilic molecules through the skin. Stable lamellae with LPP thickness are also formed via the spontaneous demixing of individual lipids, which follow with good approximation the distributions modeled from neutron diffraction (Beddoes et al, 2018;Mojumdar et al, 2015a). Such comparison is free from bias, because measurements of the LPP are not used in the simulation energy function and the initial configurations are randomized.…”

“…In samples of similar composition to the one here used, the SPP is competitive with the LPP. The SPP can be suppressed only by using higher concentrations of CER[EOS] (Beddoes et al, 2018) even when applying heat above 80 °C followed by several hours of equilibration at room temperature (a procedure used to enhance the rate of formation of the LPP). Except for the atomistic simulations shown in Fig.…”

“…To explain the LPP, a trilayer or "sandwich" model has been proposed (Beddoes et al, 2018;Bouwstra et al, 2001;Mojumdar et al, 2015a), wherein two liquid-ordered bilayers are thought to enclose a central liquid-disordered layer through which permeation may occur. NMR experiments also showed that the skin lipids are in equilibrium between "solid" and "liquid" states, with the "solid" state being dominant (Pham et al, 2017).…”

“…Groen et al, 2009;Mojumdar et al, 2015a). The interior exhibits a partially de-mixed lipid distribution characteristic of the LPP(Beddoes et al, 2018;Bouwstra et al, 2001;Mojumdar et al, 2015a), with a higher concentration of ceramides in the outer leaflets (±4 to ±6 nm), of cholesterol in the regions immediately below the outer leaflets (±2 to ±4 nm), and of fatty acids in the central region (-2 nm to +2 nm) (Figs.…”