Emanuele Panizon

Calculating the free energy of transfer of small solutes into a model lipid membrane: Comparison between metadynamics and umbrella sampling

We compare the performance of two well-established computational algorithms for the calculation of free-energy landscapes of biomolecular systems, umbrella sampling and metadynamics. We look at benchmark systems composed of polyethylene and polypropylene oligomers interacting with lipid (phosphatidylcholine) membranes, aiming at the calculation of the oligomer water-membrane free energy of transfer. We model our test systems at two different levels of description, united-atom and coarse-grained. We provide optimized parameters for the two methods at both resolutions. We devote special attention to the analysis of statistical errors in the two different methods and propose a general procedure for the error estimation in metadynamics simulations. Metadynamics and umbrella sampling yield the same estimates for the water-membrane free energy profile, but metadynamics can be more efficient, providing lower statistical uncertainties within the same simulation time.

MARTINI Coarse-Grained Models of Polyethylene and Polypropylene

The understanding of the interaction of nanoplastics with living organisms is crucial both to assess the health hazards of degraded plastics and to design functional polymer nanoparticles with biomedical applications. In this paper, we develop two coarse-grained models of everyday use polymers, polyethylene (PE) and polypropylene (PP), aimed at the study of the interaction of hydrophobic plastics with lipid membranes. The models are compatible with the popular MARTINI force field for lipids, and they are developed using both structural and thermodynamic properties as targets in the parametrization. The models are then validated by showing their reliability at reproducing structural properties of the polymers, both linear and branched, in dilute conditions, in the melt, and in a PE-PP blend. PE and PP radius of gyration is correctly reproduced in all conditions, while PE-PP interactions in the blend are slightly overestimated. Partitioning of PP and PE oligomers in phosphatidylcholine membranes as obtained at CG level reproduces well atomistic data.

Nanoscale Effects on Phase Separation

Classical nucleation theory predicts that a binary system which is immiscible in the bulk should become miscible at the nanoscale when lowering its size below a critical size. Here we tackle the problem of miscibility in nanoalloys with a combination of ab initio and atomistic calculations, developing a statistical-mechanics approach for the free energy cost of forming phase-separated aggregates. We apply it to the controversial case of AuCo nanoalloys. AuCo is immiscible in the bulk, but a rich variety of nanoparticle configurations, both phase-separated and intermixed, have been obtained experimentally. Our calculations strongly point to the permanence of an equilibrium miscibility gap down to the nanoscale and to the nonexistence of a critical size below which phase separation is impossible. We show that this is due to nanoscale effects of general character, caused by the existence of preferred nucleation sites in nanoparticles, which lower the free-energy cost for phase separation with respect to bulk systems.

Structures and segregation patterns of Ag-Cu and Ag-Ni nanoalloys adsorbed on MgO(0 0 1)

Low-energy geometric structures and segregation patterns of Ag-Cu and Ag-Ni nanoparticles adsorbed on MgO(0 0 1) are searched for by global optimisation methods within an atomistic potential model. Sizes betwen 100 and 300 atoms are considered for several compositions. In all cases, Ag segregates to the nanoparticle surface, so that Cu@Ag and Ni@Ag core-shell arrangements are found, with off-centre cores for Ag-rich compositions. The behaviours of Ag-Cu and Ag-Ni differ at the interface with the MgO substrate. For Ag-Cu, some Cu atoms are at the interface even for compositions that are very rich in Ag, where Ag-Ni nanoparticles present an interface completely made of Ag atoms. Ag-Ni and Ag-Cu also differ concerning their geometric structures. With increasing Ag content, in Ag-Cu we find the structural sequence faulted fcc [Formula: see text] icosahedral [Formula: see text] fcc, while in Ag-Ni we find the sequence hcp [Formula: see text] faulted fcc-faulted hcp [Formula: see text] icosahedral [Formula: see text] fcc.

Interaction of hydrophobic polymers with model lipid bilayers

The interaction of nanoscale synthetic materials with cell membranes is one of the key steps determining nanomaterials’ toxicity. Here we use molecular simulations, with atomistic and coarse-grained resolution, to investigate the interaction of three hydrophobic polymers with model lipid membranes. Polymer nanoparticles made of polyethylene (PE), polypropylene (PP) and polystyrene with size up to 7 nm enter easily POPC lipid membranes, localizing to the membrane hydrophobic core. For all three materials, solid polymeric nanoparticles become essentially liquid within the membrane at room temperature. Still, their behavior in the membrane core is not the same: PP and PS disperse in the core of the bilayer, while PE shows a tendency to aggregate. We also examined the interaction of the polymers with heterogeneous membranes, consisting of a ternary lipid mixture exhibiting liquid-ordered/liquid-disordered phase separation. The behavior of the three polymers is markedly different: PP disfavors lipid phase separation, PS stabilizes it, and PE modifies the topology of the phase boundaries and causes cholesterol depletion from the liquid ordered phase. Our results show that different hydrophobic polymers have major effects on the properties of lipid membranes, calling for further investigations on model systems and cell membranes.