Congratulations to Chloe Frame, Ph.D., a former member of the McCabe Lab in VINSE! Chloe鈥檚 paper, 鈥�Multiscale simulation of stratum corneum lipid mixtures: effects of ceramide headgroups on structural organization and hydrogen bonding networks,鈥� was selected for a special issue honoring pioneer skin lipid researcher Professor听Joke Bouwstra.
The outermost layer of human skin, the stratum corneum, serves as the body鈥檚 primary barrier, formed by a complex lipid matrix of ceramides, cholesterol, and free fatty acids. However, the molecular mechanisms linking lipid composition to barrier structure and function remain difficult to fully resolve experimentally.
In this work, multiscale molecular dynamics simulations were used to investigate how ceramide structure influences lipid organization and hydrogen bonding in the stratum corneum. The results show that ceramide headgroup chemistry indeed affects hydrogen bonding patterns. However, in more complex, biologically relevant mixtures, overall barrier properties are driven more strongly by lipid chain-length distribution than by hydrogen bonding alone. These findings connect molecular composition to macroscopic barrier behavior and help explain experimental observations.
Chloe Frame, Ph.D., graduated from 天美传媒官网 in May 2025 with a Ph.D. in Chemical Engineering, where she conducted her research in the lab of Professor听Clare McCabe. She is currently based in San Diego, where she works at Schr枚dinger, supporting scientists in drug discovery and material science by applying molecular modeling technologies.
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Authors: Chloe Frame, Christopher Iacovella,听David J.听Moore,听Annette L.听Bunge, and Clare听McCabe
Abstract: The barrier function of the outermost layer of human skin, the stratum corneum (SC), arises from its multilamellar lipid matrix composed primarily of ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs). Coarse-grained (CG) and atomistic molecular dynamics simulations have been used to study self-assembled multilayers comprising CERs NS, NP, AS, and AP, in pure CER systems and mixtures of CERs with CHOL and FFAs. Equilibrated CG configurations were reverse-mapped to recover atomistic details and analyzed to extract structures and hydrogen bonding. Simulations of pure CERs agreed with experimental trends: phytosphingosine CERs (NP and AP) exhibited more C鈥撯�揙 hydrogen bonds, consistent with lower amide I FTIR frequencies, than their sphingosine counterparts (NS and AS). Likewise, non-hydroxy CERs (NS and NP) exhibited more C鈥揙 hydrogen bonding than their 伪-hydroxy analogs (AS and AP). CER mixtures with CHOL and FFA showed reduced C鈥撯�揙 hydrogen bonding compared to pure CERs, though this effect depended on water content. Hydroxyl location was critical: OH on the phytosphingosine base increased C鈥撯�揙 hydrogen bonding, whereas the 伪-hydroxy on the acyl chain reduced it. In CER NP:AP mixtures with CHOL and FFA, simulations reproduced the experimental repeat distances for NP-rich and AP-rich systems despite differences in hydrogen bonding. Simulations of multicomponent mixtures resembling the SC model of Bouwstra demonstrated the dominant effect of chain-length distribution, rather than CER hydrogen bonding, on permeability. This work shows how multiscale modeling integrated with experiments can uncover molecular mechanisms linking composition and SC barrier structure to interpret experimental results.