New Coarse-Grained Models for Stratum Corneum Ceramides Reveal Headgroup-Dependent Structural Organization

Area of Science:

• Biophysics
• Materials Science
• Computational Chemistry

Background:

• The skin's barrier function relies on ordered lipids in the stratum corneum.
• Atomistic simulations are too computationally expensive for large skin lipid structures.
• Coarse-grained models offer efficiency but were limited to one ceramide type.

Purpose of the Study:

• To extend coarse-grained models to include more ceramide subclasses.
• To enable large-scale simulations of skin lipid organization.
• To investigate the impact of ceramide headgroup hydroxylation on lipid structure.

Main Methods:

• Extended a Multistate Iterative Boltzmann Inversion (MS-IBI) coarse-grained model.
• Developed models for ceramides NP, AP, and AS by transferring parameters.
• Validated models against atomistic simulations and experimental data.

Main Results:

• Successfully created coarse-grained models for additional ceramide subclasses.
• Simulated multilayers showed realistic lamellar organization and lipid packing.
• Demonstrated that headgroup hydroxylation affects ceramide tail conformation and lipid arrangement.

Conclusions:

• The MS-IBI approach is flexible and transferable for developing coarse-grained lipid models.
• New models enable large-scale simulations of complex stratum corneum lipid mixtures.
• Findings provide insights into skin barrier structure and the role of ceramide variations.