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

Jacopo Cardellini,Sebastian Salassi,Costanza Montis,Debora Berti,Enrico Lavagna,Giulia Rossi,Lucrezia Caselli

doi:10.1021/acs.jctc.1c00627

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.

Highlights

Nowadays, it is possible to functionalize Au NPs with a variety of organic ligands that confer them specific functionalities, such as the responsiveness to physical stimuli[1,2] or the ability to selectively interact with specific biological targets.[3]
The atomistic model we chose as a target for the parameterization of the coarse grained (CG) models is the all-atom OPLS force field.[27,34−36] All the details concerning the OPLS citrate model development, its validation, and further comparisons between OPLS and obtained by evaporating the solvent under a stream of nitrogen alternative atomistic force fields are reported in the Supporting and overnight vacuum drying
In this paper we developed, validated, and tested a model for capped Au NPs (CNPs) compatible with the popular Martini CG model, with the final goal to be able to simulate, by molecular dynamics (MD), the interaction between CNPs and model phospatidylcholine bilayers

Summary

Introduction

It is possible to functionalize Au NPs with a variety of organic ligands that confer them specific functionalities, such as the responsiveness to physical stimuli[1,2] or the ability to selectively interact with specific biological targets.[3] In the biomedical area, a strict requirement for Au NPs is to be dispersible and colloidally stable in aqueous environments. Colloidal stability is required from the synthesis stage to the final application. A common strategy to achieve colloidal stability is to cap the Au NP surface with sodium citrate, which can be used as a reducing agent during nanoparticle (NP) synthesis.[4] Citrate-capped Au NPs (CNPs) are commercialized with sizes ranging from a few to hundreds of nanometers in diameter. As citrate anions are noncovalently adsorbed on the

Methods

Results

Conclusion