Dumbbells, chains, and ribbons: anisotropic self-assembly of isotropic nanoparticles.

Functionalizing the surface of metal nanoparticles can assure their stability in solution or mediate their self-assembly into aggregates with controlled shapes. Here we present a computational study of the colloidal aggregation of gold nanoparticles (Au NPs) isotropically functionalized by a mixture of charged and hydrophobic ligands. We show that, by varying the relative proportion of the two ligands, the NPs form anisotropic aggregates with markedly different topologies: dumbbells, chains, or ribbons. In all cases, two kinds of connections keep the aggregates together: hydrophobic bonds and ion bridges. We show that the anisotropy of the aggregates derives from the NP shell reshaping due to the formation of the hydrophobic links, while ion bridges are accountable for the "secondary structure" of the aggregates. Our findings provide a general physical principle that can also be exploited in different self-assembled systems: anisotropic/directional aggregation can be achieved starting from isotropic objects with a soft, deformable surface.

Membrane Phase Drives the Assembly of Gold Nanoparticles on Biomimetic Lipid Bilayers.

In recent years, many efforts have been devoted to investigating the interaction of nanoparticles (NPs) with lipid biomimetic interfaces, both from a fundamental perspective aimed at understanding relevant phenomena occurring at the nanobio interface and from an application standpoint for the design of novel lipid-nanoparticle hybrid materials. In this area, recent reports have revealed that citrate-capped gold nanoparticles (AuNPs) spontaneously associate with synthetic phospholipid liposomes and, in some cases, self-assemble on the lipid bilayer. However, the mechanistic and kinetic aspects of this phenomenon are not yet completely understood. In this study, we address the kinetics of interaction of citrate-capped AuNP with lipid vesicles of different rigidities (gel-phase rigid membranes on one side and liquid-crystalline-phase soft membranes on the other). The formation of AuNP-lipid vesicle hybrids was monitored over different time and length scales, combining experiments and simulation. The very first AuNP-membrane contact was addressed through molecular dynamics simulations, while the structure, morphology, and physicochemical features of the final colloidal objects were studied through UV-visible spectroscopy, small-angle X-ray scattering, dynamic light scattering, and cryogenic electron microscopy. Our results highlight that the physical state of the membrane triggers a series of events at the colloidal length scale, which regulate the final morphology of the AuNP-lipid vesicle adducts. For lipid vesicles with soft membranes, the hybrids appear as single vesicles decorated by AuNPs, while more rigid membranes lead to flocculation with AuNPs acting as bridges between vesicles. Overall, these results contribute to a mechanistic understanding of the adhesion or self-assembly of AuNPs onto biomimetic membranes, which is relevant for phenomena occurring at the nano-bio interfaces and provide design principles to control the morphology of lipid vesicle-inorganic NP hybrid systems.

A Martini Coarse Grained Model of Citrate-Capped Gold Nanoparticles Interacting with Lipid Bilayers.

Citrate capping is one of the most common strategies to achieve the colloidal stability of Au nanoparticles (NPs) with diameters ranging from a few to hundreds of nanometers. Citrate-capped Au nanoparticles (CNPs) represent a step of the synthesis of Au NPs with specific functionalities, as CNPs can be further functionalized via ligand-exchange reactions, leading to the replacement of citrate with other organic ligands. In vitro, CNPs are also used to address the fundamental aspects of NP-membrane interactions, as they can directly interact with cells or model cell membranes. Their affinity for the bilayer is again mediated by the exchange of citrate with lipid molecules. Here, we propose a new computational model of CNPs compatible with the coarse grained Martini force field. The model, which we develop and validate through an extensive comparison with new all-atom molecular dynamics (MD) simulations and UV-vis and Fourier transform infrared spectroscopy data, is aimed at the MD simulation of the interaction between citrate-capped NPs and model phosphatidylcholine lipid membranes. As a test application we show that, during the interaction between a single CNP and a flat planar 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer, the citrate coating is spontaneously replaced by lipids on the surface of Au NPs, while the NP size and shape determine the final structural configuration of the NP-bilayer complex.

Non-disruptive uptake of anionic and cationic gold nanoparticles in neutral zwitterionic membranes.

The potential toxicity of ligand-protected nanoparticles (NPs) on biological targets is crucial for their clinical translation. A number of studies are aimed at investigating the molecular mechanisms shaping the interactions between synthetic NPs and neutral plasma membranes. The role played by the NP surface charge is still widely debated. We compare, via liposome leakage assays, the perturbation induced by the penetration of sub-6 nm anionic and cationic Au NPs into model neutral lipid membranes composed of the zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Our charged Au NPs are functionalized by a mixture of the apolar 1-octanethiol and a ω-charged thiol which is either the anionic 11-mercapto-1-undecanesulfonate or the cationic (11-mercaptoundecyl)-N,N,N-trimethylammonium. In both cases, the NP uptake in the bilayer is confirmed by quartz crystal microbalance investigations. Our leakage assays show that both negatively and positively charged Au NPs do not induce significant membrane damage on POPC liposomes when penetrating into the bilayer. By means of molecular dynamics simulations, we show that the energy barrier for membrane penetration is the same for both NPs. These results suggest that the sign of the NP surface charge, per se, does not imply different physicochemical mechanisms of interaction with zwitterionic lipid membranes.

Amphiphilic gold nanoparticles perturb phase separation in multidomain lipid membranes.

Amphiphilic gold nanoparticles with diameters in the 2-4 nm range are promising as theranostic agents thanks to their spontaneous translocation through cell membranes. This study addresses the effects that these nanoparticles may have on a distinct feature of plasma membranes: lipid lateral phase separation. Atomic force microscopy, quartz crystal microbalance, and molecular dynamics are combined to study the interaction between model neuronal membranes, which spontaneously form ordered and disordered lipid domains, and amphiphilic gold nanoparticles having negatively charged surface functionalization. Nanoparticles are found to interact with the bilayer and form bilayer-embedded ordered aggregates. Nanoparticles also suppress lipid phase separation, in a concentration-dependent fashion. A general, yet simple thermodynamic model is developed to show that the change of lipid-lipid enthalpy is the dominant driving force towards the nanoparticle-induced destabilization of phase separation.

Water dynamics affects thermal transport at the surface of hydrophobic and hydrophilic irradiated nanoparticles.

Plasmonic nanoparticles, such as Au nanoparticles (NPs) coated with bio-compatible ligands, are largely studied and tested in nanomedicine for photothermal therapies. Nevertheless, no clear physical interpretation is currently available to explain thermal transport at the nanoparticle surface, where a solid-liquid (core-ligand) interface is coupled to a liquid-liquid (ligand-solvent) interface. This lack of understanding makes it difficult to control the temperature increase imposed by the irradiated NPs to the surrounding biological environment, and it has so far hindered the rational design of the NP surface chemistry. Here, atomistic molecular dynamics simulations are used to show that thermal transport at the nanoparticle surface depends dramatically on solvent diffusivity at the ligand-solvent interface. Furthermore, using physical indicators of water confinement around hydrophobic and hydrophilic ligands, a predictive model is developed to allow the engineering of NP coatings with the desired thermal conductivities at the nanoscale.

Tailored Ag-Cu-Mg multielemental nanoparticles for wide-spectrum antibacterial coating.

Bactericidal nanoparticle coatings are very promising for hindering the indirect transmission of pathogens through cross-contaminated surfaces. The challenge, limiting their employment in nosocomial environments, is the ability of tailoring the coating's physicochemical properties, namely, composition, cytotoxicity, bactericidal spectrum, adhesion to the substrate, and consequent nanoparticles release into the environment. We have engineered a new family of nanoparticle-based bactericidal coatings comprising Ag, Cu, and Mg and synthesized by a green gas-phase technique. These coatings present wide-spectrum bactericidal activity on both Gram-positive and Gram-negative reference strains and tunable physicochemical properties of relevance in view of their "on-field" deployment. The link between material and functional properties is rationalized based on a multidisciplinary and multitechnique approach. Our results pave the way for engineering biofunctional, fully tunable nanoparticle coatings, exploiting an arbitrarily wide number of elements in a straightforward, eco-friendly, high-throughput, one-step process.

Anionic nanoparticle-lipid membrane interactions: the protonation of anionic ligands at the membrane surface reduces membrane disruption.

Monolayer-protected gold nanoparticles (Au NPs) are promising biomedical tools with applications in diagnosis and therapy, thanks to their biocompatibility and versatility. Here we show how the NP surface functionalization can drive the mechanism of interaction with lipid membranes. In particular, we show that the spontaneous protonation of anionic carboxylic groups on the NP surface can make the NP-membrane interaction faster and less disruptive.