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

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.

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

“…Our simulations rely on a recently developed coarse-grained model of citrate-capped Au NPs. 37 We have considered two models for the NP. Most of the simulations contain a NP that has a diameter of 8 nm.…”

“… 43 The AuNP citrate coverage in our simulations is 0.97÷1.4 citrate/nm 2 , which is consistent with the available experimental literature. 37 In ref ( 37 ) we calculated the free energy profile for the adsorption of citrate and POPC on the surface of a Au nanoparticle, showing that the interaction with the lipid was thermodynamically favored. Consistently, we observed the spontaneous penetration of Au NPs into POPC fluid bilayers.…”

“…The model for the NPs and citrate was custom developed and described in a previous work. 37 For Au nanoparticles, we used a 1:1 atom-to-bead mapping scheme, and the Lennard-Jones parameters of the Au–Au interaction were set to the Heinz nonpolarizable potential. 38 We used two models of Au NPs, both in the shape of a truncated octahedron with diameters of about 8 (12934 beads) and 14 nm (69473 beads).…”

“…The model for the NPs and citrate was custom developed and described in a previous work . For Au nanoparticles, we used a 1:1 atom-to-bead mapping scheme, and the Lennard-Jones parameters of the Au–Au interaction were set to the Heinz nonpolarizable potential .…”

Interaction of Metallic Nanoparticles With Biomimetic Lipid Liquid Crystalline Cubic Interfaces

“…In recent works, a combination of computational and experimental results highlighted that the spontaneous aggregation of citrated AuNPs on vesicles of lamellar nature is triggered by the fast release of citrate anions at the AuNPs surface ( Montis et al, 2020b ; Salassi et al, 2021 ; Cardellini et al, 2022 ). Such release occurs upon adhesion of AuNPs to the vesicles’ membrane, which drives the displacement of citrate anions by the lipids composing the vesicles’ membrane (i.e., a citrate/lipid ligand exchange).…”