MARTIN, M. | bioRxiv Science

bioRxiv2025

Predicting non-covalent interactions between antioxidants in biological membranes through molecular dynamics

The synergistic association of different polyphenols has gained much interest in the food industry to develop efficient antioxidant cocktails, reducing the concentration of active agents and subsequently potential toxicity. The theoretical description and prediction of such processes is of central interest in this development. This study aims at benchmarking the performance of molecular dynamics (MD) to predict the formation of non-covalent complexes between {pi}-conjugated antioxidants, including two prototypes (quercetin and vitamin E), in a pure 1,2-dipalmitoylphosphatidylcholine (DOPC) lipid bilayer. To reproduce the experimentally observed quenching of vitamin E fluorescence by quercetin, a sphere-of-action quenching model was applied. The predictive capability of MD simulations at capturing this non-covalent association was evaluated with five other {pi}-conjugated potential partners of vitamin E, namely catechin, caffeic acid, myricetin, kaempferol, and galangin. The observed trend agreed with experimental studies, validating again the use of MD simulations as a tool to measure the potential synergism between natural antioxidants.

bioinformatics↗

bioRxiv2024

Skin hydration by natural moisturizing factors, a story of H-bond networking

Dry skin is a common condition experienced by many. Besides being particularly present during the cold season, various diseases exist all year round, leading to localized xerosis. To prevent it, the skin is provided with natural moisturizing factors (NMFs). They are small amino acids or derivatives found in the outermost layer of the skin, the stratum corneum (SC). They are often claimed to be highly efficient humectants, increasing the water content to maintain the fluidity of the skin. However, alternative mechanisms have been proposed, suggesting that NMFs themselves may act as lipid mobility amplifiers. This work aims at investigating the role of three NMFs, namely urea (URE), glycerol (GLY) and urocanic acid / urocanate (UCA/UCO) in SC in silico models, considering two different levels of humidity. Molecular dynamic simulations showed an increase in the diffusion of different lipid components, mainly free fatty acids (FFAs) and ceramides acyl chain moieties, in the presence of either high water content or NMFs. The membrane properties were modified, as seen by an increased thickness and a greater lateral stiffness. All NMFs exhibited a similar impact, whereas UCA revealed slight differences according to its charged state. By studying NMF-water intermolecular interactions, we highlighted the role of NMF as a regulator of membrane perturbations, while insuring membrane fluidity. This role allows NMFs to prevent destabilization of the skin membrane in the presence of high-water content. This study, performed at an atomistic resolution, highlighted a strong H-bond network between lipids, involving mainly ceramides but also all other components. This network can be modified in the presence of high-water concentration or NMFs, resulting in modifications of membrane properties, rationalizing hydration effects.

bioinformatics↗