# Insights into skin barrier function: In silico and experimental studies of healthy and diseased stratum corneum lipid models

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $290,406

## Abstract

Skin’s function as a barrier to infection, dehydration and chemical assault is critical to health and survival. Its
barrier effectiveness rests almost entirely in the thin, outer membrane, called the stratum corneum (SC), which
consists of dead skin cells embedded in a highly organized dense lipid-rich environment. This organization of
the SC lipids into ordered gel or crystalline phases can be ascribed to its unique composition: mostly
ceramides, free fatty acids and cholesterol, with no phospholipids in contrast to most biological membranes.
There is compelling evidence that an impaired skin barrier, which is coincidental with abnormalities in
composition, organization and structure of the SC lipids, is the primary event in the pathogenesis of skin
disease and even some systemic diseases (e.g., the occurrence of asthma and allergic rhinitis in patients with
atopic dermatitis). In contrast, the effectiveness of the SC barrier is a central problem limiting topical and
transdermal drug delivery. An improved understanding of the relationship between SC lipid composition,
structure, and organization and barrier function is needed: (1) to understand the relationship between skin
disease, reduced barrier function, and effective treatment, and (2) to develop new techniques for either
reducing barrier function (to deliver drugs more effectively) or improving it (to protect against disease, toxic
exposure and water loss). While experimental lipid systems that mimic the SC can be designed and studied,
any understanding of the relationship between barrier function and lipid composition and organization can only
be inferred; accurate computational studies on well-characterized systems would allow the mechanistic basis
of these relationships to be clearly probed. To complement existing model lipid systems that mimic healthy SC,
we will experimentally design and characterize new model lipid systems that mimics diseased skin, specifically
atopic dermatitis (AD). These well-characterized synthetic lipid models will form the basis of the systems to be
explored computationally. Using a multi-scale modeling approach that seamlessly combines simulations at the
atomistic and coarse-grained (CG) levels, unprecedented insight into the molecular level organization of, and
interactions between, SC lipid molecules in equilibrated assemblies of SC lipids modeling normal and AD-SC
will be obtained. Targeted experiments will also be performed to provide the data needed to validate the model
predictions (structures of the simulated lipid assemblies will be compared with spectroscopic, scattering and
permeability studies on the corresponding experimental systems) before the computational framework is used
for predictive in silico screening to probe various hypothesis related to barrier function and determine the
sensitivity of the SC structure and thus barrier function to changes in lipid composition. In contrast to
experimental studies, the computational models allow for var...

## Key facts

- **NIH application ID:** 10261444
- **Project number:** 5R01AR072679-04
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Clare McCabe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $290,406
- **Award type:** 5
- **Project period:** 2018-08-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261444

## Citation

> US National Institutes of Health, RePORTER application 10261444, Insights into skin barrier function: In silico and experimental studies of healthy and diseased stratum corneum lipid models (5R01AR072679-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10261444. Licensed CC0.

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