Topology matters: Cyclic Peptide Permeate Skin-Membrane Mimics More Easily Than Linear Analog
Introduction
The outer skin barrier limits the diffusion of most molecules. Using tailored stratum corneum models based on precise lipidomics, we compared cyclic and linear peptide analogs.
Our advanced simulation workflow revealed distinct differences in conformational stability, hydration, and passive permeability.
Methods
Peptide Modeling
Environment Modeling
- ⇒ Sterols
- ⇒ Ceramides
- ⇒ Free fatty acids
- x Cardiolipins
- x Phospholipids
- x Phosphosphingolipids
Stratum Corneum
Biased MD Simulations
In standard MD simulations, molecules evolve naturally, but rare events like observing a membrane or binding can take too long. Biased MD adds a steering force to accelerate these processes, making it possible to quantify their likelihood through the free energy landscape.
Permeability Assessment
D refers to the diffusion coefficient
P refers to the permeability coefficient
Deliverables
- Key Quantitative Descriptors:
- Free Energy (FE),
- Permeability coefficient (log P)
- Molecular mechanisms
- Optimization strategy
Results & Discussions
The cyclic peptide remained compact and rigid. In contrast, the linear analog explored a wider conformational space, from extended to U-shaped structures, which slowed its passive permeation. The 2D plot (on the right) of molecular extension vs. insertion depth highlights these differences: the cyclic peptide maintained a stable structure during permeation, whereas the linear analog underwent conformational changes that affected its hydration state and thus its permeation. Permeability analysis confirmed that the cyclic form is vastly more permeable, with log P values differing by about 19 orders of magnitude.
This study was conduct by : Lucas Meyer
Lucas Meyer Cosmetics develops and supplies high-value active, functional, and delivery-system ingredients for the cosmetics and personal-care industry, grounded in robust research and formulation science. Their scientific work leverages expertise in phospholipids, botanical extracts, peptides and biotechnology to design ingredients that support skin and hair health—targeting issues like aging, environmental stress, barrier function, and inflammation. he company maintains global R&D and application labs that help transform raw actives into stable, effective, market-ready formulations, offering technical and regulatory support alongside innovation. Through a science-driven, sustainability-conscious approach, Lucas Meyer Cosmetics aims to deliver cosmetic solutions that combine efficacy, safety, and respect for natural skin physiology.
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