Using molecular simulation to understand the skin barrier

Parashara Shamaprasad, Chloe O. Frame, Timothy C. Moore, Alexander Yang, Christopher R. Iacovella, Joke A. Bouwstra, Annette L. Bunge, Clare McCabe*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

14 Citations (Scopus)
99 Downloads (Pure)


Skin's effectiveness as a barrier to permeation of water and other chemicals rests almost entirely in the outermost layer of the epidermis, the stratum corneum (SC), which consists of layers of corneocytes surrounded by highly organized lipid lamellae. As the only continuous path through the SC, transdermal permeation necessarily involves diffusion through these lipid layers. The role of the SC as a protective barrier is supported by its exceptional lipid composition consisting of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs) and the complete absence of phospholipids, which are present in most biological membranes. Molecular simulation, which provides molecular level detail of lipid configurations that can be connected with barrier function, has become a popular tool for studying SC lipid systems. We review this ever-increasing body of literature with the goals of (1) enabling the experimental skin community to understand, interpret and use the information generated from the simulations, (2) providing simulation experts with a solid background in the chemistry of SC lipids including the composition, structure and organization, and barrier function, and (3) presenting a state of the art picture of the field of SC lipid simulations, highlighting the difficulties and best practices for studying these systems, to encourage the generation of robust reproducible studies in the future. This review describes molecular simulation methodology and then critically examines results derived from simulations using atomistic and then coarse-grained models.

Original languageEnglish
Article number101184
JournalProgress in Lipid Research
Early online date19 Aug 2022
Publication statusPublished - Nov 2022


  • Atomistic simulation
  • Coarse-grained models
  • Molecular dynamics simulation
  • Percutaneous permeability
  • Skin barrier function
  • Stratum corneum lipids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology


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