Molecular model for the self-assembly of the cyclic lipodepsipeptide pseudodesmin A

Self-assembly of peptides into supramolecular structures represents an active field of research with potential applications ranging from material science to medicine. Their study typically involves the application of a large toolbox of spectroscopic and imaging techniques. However, quite often, the structural aspects remain underexposed. Besides, molecular modeling of the self-assembly process is usually difficult to handle, since a vast conformational space has to be sampled. Here, we have used an approach that combines short molecular dynamics simulations for peptide dimerization and NMR restraints to build a model of the supramolecular structure from the dimeric units. Experimental NMR data notably provide crucial information about the conformation of the monomeric units, the supramolecular assembly dimensions, and the orientation of the individual peptides within the assembly. This in silico/in vitro mixed approach enables us to define accurate atomistic models of supramolecular structures of the bacterial cyclic lipodepsipeptide pseudodesmin A

How different serols contribute to cytotoxic action of sea cucumber saponins

Saponins form a diverse class of secondary metabolites found in both plants and some marine invertebrates. Holothuroids, or sea cucumbers, produce these molecules as a chemical defense against predators and parasites, but interestingly, tolerate the cytotoxic nature of these chemicals. This tolerance is poorly understood. The aim of this study was therefore to elucidate the mechanisms behind the tolerance of holothuroid cells to the cytotoxic saponins (e.g. Frondoside A) they produce. This investigation was conducted using a suite of complementary biophysical tools, firstly using in vitro techniques such as Isothermal Titration Calorimetry (ITC) and calcein leakage experiments, for measuring interactions between lipid models of various compositions and the saponin Frondoside A, then using in silico approaches such as docking methods and insertion into implicit lipid bilayers, to provide a molecular point of view on our observations. Interactions between Frondoside A and cholesterol were more favorable than those with the holothuroid Δ7 and Δ9(11) sterols. Liposomes containing cholesterol resulted in exothermic interactions with the holothuroid saponin Frondoside A whereas liposomes containing the Δ7 sterol resulted in endothermic interactions. Lipid phase simulations using settings previously developed for plant saponins revealed that the holothuroid saponin Frondoside A has an agglomerating effect on cholesterol domains, similar to that previously observed for the plant saponin α-Hederin. However, when interacting with the Δ7 sterols, the sterol domains were fragmented into small clusters. A significantly lower leakage was observed with liposomes containing the Δ7 holothuroid sterol than that with liposomes containing cholesterol. Our results suggest that the structural peculiarities of holothuroid sterols provide the organisms with a mechanism to mitigate the sterol-agglomerating effect of saponins on the cell membranes, and therefore to protect sea cucumber cells from the cytotoxicity of the saponins they produce

Development of asymmetric liposomes to mimic plant plasma membrane using cyclodextrins as lipid carriers Influence of phospholipid fatty acid chains

peer reviewedAlthough liposomes can be criticized in terms of relevance to mimic real biological membranes, they give access to information at molecular or atomistic levels that are difficult to study in cellulo. In biophysical studies on liposomes, the asymmetric nature of the lipid distribution is often overlooked despite its role in several biological mechanisms. However, in the last decades, the preparation of asymmetric liposomes has been developed especially through protocols based on lipid-exchange lead by cyclodextrins, hemifusion or inverted emulsion phase transfer approaches. These strategies focused on human plasma membrane (PM) whereas the field of plant PM asymmetric liposomes remains unexplored. One difference between these two membranes concerns their phospholipids fatty acid compositions where linoleoyl chain is widely found in plants. Hence, phospholipids containing these chain (e.g. PLPC) is favoured to build artificial plant PM in comparison with those having oleoyl structure (e.g. POPC). The main objective of this work was to elaborate preliminary asymmetric liposomes mimicking plant PM and containing charged and uncharged phospholipids. We developed asymmetric models containing phosphatidylcholine and phosphatidylserine or phosphatidylcholine and phosphatidylglycerol using methyl-β-cyclodextrins as lipid carrier. The asymmetry has been controlled using F2N12S, a fluorescent probe sensitive to outer leaflet surface charge and lipid order. We found that the exchange efficiency is directly impacted by the nature of hydrophobic chains. Indeed, asymmetric liposomes have been prepared using exchanges between phospholipids with oleyl chain whereas no exchange has been observed in the case of phospholipids containing linoleoyl chain. Based on these results, we discussed on the relevance of the cyclodextrin mediated lipid exchange strategy to produce asymmetric liposomes mimicking plant PM

Use of molecular dynamics simulations to study the interactions between barley allelochemicals and plant plasma membrane

Gramine and hordenine, two alkaloids produced by barley, were shown to inhibit the growth of a common weed (Matricaria recutita L.). This feature could be useful in order to reach a more sustainable weeds management. In vitro experiments have proven that both molecules do interact with lipid bilayers (made of a phosphatidylglycerol (PG) lipid) mimicking plant plasma membranes and are able to modify some of their properties. Moreover, gramine was shown to be more effective than hordenine in both inhibiting weeds growth and altering lipid bilayers properties, suggesting that interactions with membranes could be linked to their mode of action. Molecular dynamics (MD) simulations are carried out in order to get an insight into the molecular mechanisms that underlie these interactions with model membranes and to discriminate between gramine behavior and hordenine behavior

Enzymatically-synthesized xylo-oligosaccharides laurate esters as surfactants of interest

Lipase-catalyzed synthesis of xylo-oligosaccharides esters from pure xylobiose, xylotriose and xylotetraose in the presence of vinyl laurate was investigated. The influence of different experimental parameters such as the loading of lipase, the reaction duration or the use of a co-solvent was studied and the reaction conditions were optimized with xylobiose. Under the best conditions, a regioselective esterification occurred to yield a monoester with the acyl chain at the OH-4 of the xylose unit at the non-reducing end. Surface-active properties of these pure xylo-oligosaccharides fatty esters have been evaluated. They display interesting surfactant activities that differ according to the degree of polymerization (DP) of the glycone moiety. © 202