Quercetin (3,3ʹ,4ʹ,5,7-pentahydroxyl-flavone) is a natural flavonoid with many valuable biological effects, but its solubility in water is low, posing major limitations in applications. Quercetin encapsulation in liposomes increases its bioavailability; the drug effect on liposome elastic properties is required for formulation development. Here, we quantify the effect of quercetin molecules on the rigidity of lipoid E80 liposomes using atomic force microscopy (AFM) and molecular dynamics (MD) simulations. AFM images show no effect of quercetin molecules on liposomes morphology and structure. However, AFM force curves suggest that quercetin softens lipid membranes; the Young modulus measured for liposomes encapsulating quercetin is smaller than that determined for blank liposomes. We then used MD simulations to interpret the effect of quercetin on membrane rigidity in terms of molecular interactions. The decrease in membrane rigidity was confirmed by the simulations, which also revealed that quercetin affects structural and dynamic properties: membrane thickness is decreased, acyl chains disorder is increased, and diffusion coefficients of lipid molecules are also increased. Such changes appear to be related to the preferential localization of quercetin within the membrane, near the interface between the hydrophobic core and polar head groups of the lipids.
The Martini model is a coarse-grained force field allowing simulations of biomolecular systems as well as a range of materials, including different types of nanomaterials of technological interest. Recently, a new version of the force field (version 3) has been released, that includes new parameters for lipids, proteins, carbohydrates, and a number of small molecules, but not yet carbon nanomaterials. Here, we present new Martini models for three major types of carbon nanomaterials: fullerene, carbon nanotubes, and graphene. The new models were parameterized within the Martini 3 framework, and reproduce semi-quantitatively a range of properties for each material. In particular, the model of fullerene yields excellent solid-state properties and good properties in solution, including correct trends in partitioning between different solvents and realistic translocation across lipid membranes. The models of carbon nanotubes reproduce the atomistic behavior of nanotube porins spanning lipid bilayers. The model of graphene reproduces structural and elastic properties, as well as trends in experimental adsorption enthalpies of organic molecules. All new models can be used in large-scale simulations to study the interaction with the wide variety of molecules already available in the Martini 3 force field, including biomolecular and synthetic systems.
Equilibrated POPC lipid bilayer simulation ran with Gromacs 4.5, Orange, 50ns, T=298K, 72 POPC molecules, 2880 water molecules. This data is used in the NMRLipids II project (nmrlipids.blospot.fi, https://github.com/NMRLipids/lipid_ionINTERACTION). The Orange model is unpublished lipid model developed by Luca Monticelli et al. http://perso.ibcp.fr/luca.monticelli/research/index.html. Beta version of the model is used here, thus only trajectory is shared.
Equilibrated POPC lipid bilayer simulation ran with Gromacs 4.5, Orange, 120ns, T=298K, 72 POPC molecules, 2802 water molecules, 26 Na molecules, 26 Cl molecules. This data is used in the NMRLipids II project (nmrlipids.blospot.fi, https://github.com/NMRLipids/lipid_ionINTERACTION). The Orange model is unpublished lipid model developed by Luca Monticelli et al. http://perso.ibcp.fr/luca.monticelli/research/index.html. Beta version of the model is used here, thus only trajectory is shared.
Lipid membranes are central to cellular life. Complementing experiments, computational modeling has been essential in unraveling complex lipid-biomolecule interactions, crucial in both academia and industry. The Martini model, a coarse-grained force field for efficient molecular dynamics simulations, is widely used to study membrane phenomena but has faced limitations, particularly in capturing realistic lipid phase behavior. Here, we present refined Martini 3 lipid models with a mapping scheme that distinguishes lipid tails differing by just two carbon atoms, enhancing structural resolution and thermodynamic accuracy of model membrane systems including ternary mixtures. The expanded Martini lipid library includes thousands of models, enabling simulations of complex and biologically relevant systems. These advancements establish Martini as a robust platform for lipid-based simulations across diverse fields.
