ABSTRACT
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.
ABSTRACT
Functional peptides are now widely used in a myriad of biomedical and clinical contexts, from cancer therapy and tumor targeting to the treatment of bacterial and viral infections. Underlying this diverse range of applications are the non-specific interactions that can occur between peptides and cell membranes, which, in many contexts, result in spontaneous internalization of the peptide within cells by avoiding energy-driven endocytosis. For this to occur, the amphipathicity and surface structural flexibility of the peptides play a crucial role and can be regulated by the presence of specific molecular residues that give rise to precise molecular events. Nevertheless, most of the mechanistic details regulating the encounter between peptides and the membranes of bacterial or animal cells are still poorly understood, thus greatly limiting the biomimetic potential of these therapeutic molecules. In this arena, finely engineered nanomaterials-such as small amphiphilic gold nanoparticles (AuNPs) protected by a mixed thiol monolayer-can provide a powerful tool for mimicking and investigating the physicochemical processes underlying peptide-lipid interactions. Within this perspective, we present here a critical review of membrane effects induced by both amphiphilic AuNPs and well-known amphiphilic peptide families, such as cell-penetrating peptides and antimicrobial peptides. Our discussion is focused particularly on the effects provoked on widely studied model cell membranes, such as supported lipid bilayers and lipid vesicles. Remarkable similarities in the peptide or nanoparticle membrane behavior are critically analyzed. Overall, our work provides an overview of the use of amphiphilic AuNPs as a highly promising tailor-made model to decipher the molecular events behind non-specific peptide-lipid interactions and highlights the main affinities observed both theoretically and experimentally. The knowledge resulting from this biomimetic approach could pave the way for the design of synthetic peptides with tailored functionalities for next-generation biomedical applications, such as highly efficient intracellular delivery systems.
ABSTRACT
The control of the aggregation of biomedical nanoparticles (NP) in physiological conditions is crucial as clustering may change completely the way they interact with the biological environment. Here we show that Au nanoparticles, functionalized by an anionic, amphiphilic shell, spontaneously aggregate in fluid zwitterionic lipid bilayers. We use molecular dynamics and enhanced sampling techniques to disentangle the short-range and long-range driving forces of aggregation. At short inter-particle distances, ion-mediated, charge-charge interactions (ion bridging) stabilize the formation of large NP aggregates, as confirmed by cryo-electron microscopy. Lipid depletion and membrane curvature are the main membrane deformations driving long-range NP-NP attraction. Ion bridging, lipid depletion, and membrane curvature stem from the configurational flexibility of the nanoparticle shell. Our simulations show, more in general, that the aggregation of same-charge membrane inclusions can be expected as a result of intrinsically nanoscale effects taking place at the NP-NP and NP-bilayer soft interfaces.
Subject(s)
Metal Nanoparticles , Nanoparticles , Cryoelectron Microscopy , Gold , Lipid Bilayers , MembranesABSTRACT
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.
ABSTRACT
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.
ABSTRACT
The aggregation of nanoparticles affects their reactivity, transport across biological membranes, uptake into cells, toxicity, and fate in the environment. In the case of membrane-embedded, hydrophobic nanoparticles the relationship between size and aggregation pattern is not well understood. Here, we explore this relationship for the case of spherically symmetrical nanoparticles using the MARTINI coarse-grained force field. We find that the free energy of dimerization depends strongly on nanoparticle size: the smallest molecules (mimicking C60 fullerene) aggregate only weakly, the largest ones form large three-dimensional aggregates causing major deformations in the host membrane, and the intermediate-sized particles show a tendency to form linear aggregates. Suppressing membrane undulations reduces very significantly aggregation, and substantially abolishes linear aggregation, suggesting a relationship between membrane curvature and aggregation geometry. At low concentration, when placed on membranes of variable curvature, the intermediate size nanoparticles move rapidly to high curvature regions - suggesting that they can sense membrane curvature. At high concentration, the same nanoparticles induce massive membrane deformations, without affecting the mechanical stability of the membrane - suggesting that they can generate membrane curvature.