Biology subjects

Chantemargue, B.

Publications and source records attributed to Chantemargue, B..

4 recordsLinked to original sources

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↗

bioRxiv2022

Insights into the structure and function of the human organic anion transporter 1 in lipid bilayer membranes

The human SLC22A6/OAT1 plays an important role in the elimination of a broad range of endogenous substances and xenobiotics thus attracting attention from the pharmacological community. Furthermore, OAT1 is also involved in key physiological events such as the remote inter-organ communication. Despite its significance, the knowledge about hOAT1 structure and the transport mechanism at the atomic level remains fragmented owing to the lack of resolved structures. By means of protein-threading modeling refined by s-scaled Molecular Dynamics simulations, the present study provides the first robust model of hOAT1 in outward-facing conformation. Taking advantage of the AlphaFold 2 predicted structure of hOAT1 in inward-facing conformation, we here provide the essential structural and functional features comparing both states. The intracellular motifs conserved among Major Facilitator Superfamily members create a so-called "charge-relay system" that works as molecular switches modulating the conformation. The principal element of the event points at interactions of charged residues that appear crucial for the transporter dynamics and function. Moreover, hOAT1 model was embedded in different lipid bilayer membranes highlighting the crucial structural dependence on lipid-protein interactions. MD simulations supported the pivotal role of phosphatidylethanolamine components to the protein conformation stability. The present model is made available to decipher the impact of any observed polymorphism and mutation on drug transport as well as to understand substrate binding modes.

pharmacology and toxicology↗

bioRxiv2018

Nitrone-Trolox conjugate as an inhibitor of lipid oxidation: Towards synergistic antioxidant effects

1Free radical scavengers like -phenyl-N-tert-butylnitrone (PBN) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) have been widely used as protective agents in various biomimetic and biological models. A series of three amphiphilic Trolox and PBN derivatives have been designed by adding to the parent molecules both a perfluorinated chain and a sugar group in order to render them amphiphilic. In this work, we have studied the interaction of these derivatives with lipid membranes and how it correlates to their antioxidant properties.\n\nThe three derivatives form monolayers at the air/water interface. We next investigated the ability of each derivative to interact with 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as well as their efficiency to inhibit the AAPH-induced oxidation of DLPC liposomes. The location of these derivatives in the membrane is a key parameter to rationalize their antioxidant efficiency. The derivative bearing both the PBN and the Trolox antioxidant moieties on the same fluorinated carrier exhibited a synergistic antioxidant effect by delaying the oxidation process. Molecular dynamics (MD) simulations supported the understanding of the mechanism of action, highlighting various key physical-chemical descriptors.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC=\"FIGDIR/small/323386_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (20K):\norg.highwire.dtl.DTLVardef@15e2ce5org.highwire.dtl.DTLVardef@1d58ee3org.highwire.dtl.DTLVardef@197f9d2org.highwire.dtl.DTLVardef@9279ff_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights- Amphiphilic fluorinated antioxidants efficiently inhibit lipid oxidation\n- The perfluorinated chain allows the insertion into membranes\n- The nature of the antioxidant is a key parameter in the antioxidant efficiency\n- The combination of Trolox and PBN results in a synergistic antioxidant effect\n\n\nCondensed running titleTrolox derivatives limit lipid oxidation

biophysics↗