Abstract
The skin’s barrier ability is an essential function for terrestrial survival, which is controlled by intercellular lipids within the stratum corneum (SC) layer. In this barrier, free fatty acids (FFAs) are an important lipid class. As seen in inflammatory skin diseases, when the lipid chain length is reduced, a reduction in the barrier’s performance is observed. In this study, we have investigated the contributing effects of various FFA chain lengths on the lamellar phase, lateral packing. The repeat distance of the lamellar phase increased with FFA chain length (C20–C28), while shorter FFAs (C16 to C18) had the opposite behaviour. While the lateral packing was affected, the orthorhombic to hexagonal to fluid phase transitions were not affected by the FFA chain length. Porcine SC lipid composition mimicking model was then used to investigate the proportional effect of shorter FFA C16, up to 50% content of the total FFA mixture. At this level, no difference in the overall lamellar phases and lateral packing was observed, while a significant increase in the water permeability was detected. Our results demonstrate a FFA C16 threshold that must be exceeded before the structure and barrier function of the long periodicity phase (LPP) is affected. These results are important to understand the lipid behaviour in this unique LPP structure as well as for the understanding, treatment, and development of inflammatory skin conditions.
Highlights
The skin has the task of protecting the body from external influences and assisting in maintaining a homeostatic environment within the body [1]
We have studied how each of the major free fatty acids (FFAs) chain lengths, observed in both healthy and diseased skin, affect the lipid organization and barrier function with the use of long periodicity phase (LPP) lipid models
Chain length the LPP repeat distance decreases; this is only true for models containing a FFA length varying between C20 and C28
Summary
The skin has the task of protecting the body from external influences and assisting in maintaining a homeostatic environment within the body [1]. The lipid matrix is comprised of three major lipid classes, ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs), at approximately equimolar ratios These extracellular lipids form two distinct co-existing crystalline lamellar structures with repeat distances of approximately 13 and 6 nm, which are referred to as the long and short periodicity phases (LPP and SPP, respectively) [3,4]. Within these lamellar structures, the majority of the SC lipids adopt a highly dense orthorhombic lateral phase, with a small proportion in the hexagonal or fluid phase [5,6]. CERs and CHOL can form the LPP [7,8,9,10]; FFAs are required for an optimal orthorhombic lateral packing [11]
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