ARTICLE: Models to Study Skin Lipids in Relation to the Barrier Function: A Modern Update on Models and Methodologies Evaluating Skin Barrier Function

April 2021 | Volume 20 | Issue 4 | Supplement Individual Articles | s10 | Copyright © April 2021

Published online April 6, 2021

Rebecca Barresi , Hawasatu Dumbuya PhD, Xue Liu PhD, I-Chien Liao PhD

L’Oréal Research and Innovation, Clark, NJ

The skin barrier is a multifaceted microenvironment, comprised not only of structural and molecular components that maintain its integrity, but also a lipid matrix comprising an equimolar ratio of cholesterol, free fatty acids, and ceramides. Lipid abnormalities induced by environmental or pathological stimuli are often associated with impaired skin barrier function and integrity. Incorporation of skin lipids in skincare formulations to help fortify barrier function has become widespread. While there are resources available to study the barrier, a comprehensive evaluation of skin models, from in situ to in vivo, that focus on alterations of the lipid content, seems to be lacking. This article reviews current methods to evaluate the skin lipid barrier and touches upon the significance of using such models within the cosmetic field to study formulations that incorporate barrier lipids.

J Drugs Dermatol. 20(4 Suppl):s10-16. doi:10.36849/JDD.S589B


The human skin is critical in protecting internal organs from exogenous factors to maintain homeostasis by contributing to a multifaceted structure known as the skin barrier. The stratum corneum (SC), or the skin’s first line of barrier protection, is comprised of corneocytes embedded within a lipid matrix. The lipid matrix in healthy skin tissue comprises an equimolar ratio of cholesterol (CHOL), free fatty acids (FFAs), ceramides (CERs), and sterol/wax esters.1 Functionally, CERs maintain and influence the barrier integrity of the skin by forming the skin lipid membrane and regulating cellular processes.1

Impaired barrier function relating to changes in skin CER concentration can be a direct result of environmental or pathological factors. The incorporation of CERs and skin lipids into formulas for moisturizers has become increasingly popular across the cosmetics and skin care field to enforce barrier integrity. Knowledge surrounding the skin barrier is continuously developing through the use of novel models and studies. This review addresses the field’s lacking comprehensive evaluation of skin models to study barrier function, particularly with application for barrier restoration and proper delivery of essential skin lipids in the cosmetic field.

In Situ Models
Lipid Model Membranes
Lipid Composition Mixtures
Lipid model membranes study the functionality of particular CERs in relation to the skin barrier. Such membranes are prepared using synthetic CERs or CERs isolated from native SC. Synthetic CERs have been shown to mimic the lipid organization of native human skin through small and wide angle x-ray diffraction.2 The function of particular lipids in barrier function is elucidated by different types of lipid mixture models. For example, ternary and quaternary lipid mixtures incorporate one or two specific CER types in conjunction with a fatty acid and CHOL. These types of models have demonstrated phase separation, whereas in vivo, the CER subclass and chain length variety protects proper structure. Simple lipid mixtures are not ideal for studying lipid phase structures, as demonstrated by mixtures lacking CER[EOS], which cannot form long phase periodicity.3

Multicomponent lipid mixtures allow for the evaluation of lipid phase behaviors in addition to studying the function of specific CERs. Short periodicity of lipid mixtures was previously studied using neutron diffraction methods.4 Multi-component lipid mixtures have shown the significance of FFAs in forming the short phase periodicity and promoting orthorhombic packing.5

The function of specific CERs incorporated the lipid mixtures helps to link specific CERs with diseased-state skin or an impaired barrier. Low and wide angle x-ray diffraction demonstrated that although the removal of some CER subclasses, like CER[EOS], is responsible for phase changes, exclusion of other subclasses does not necessarily affect the lipid organization.2 Infrared spectroscopy has also been used to study the effect of lipid ratios on crystalline lattices by varying the FFA levels in lipid mixtures. It was found that lower FFA levels favored a combination of hexagonal and orthorhombic packing, while the equimolar ratio favors solely orthorhombic packing.6