Better understanding of nanoparticles: Small Gold with a Big Future

Nanotoxicity studies are of great complexity, partly due to the fact that in vitro observations of toxicity are often not representative nor directly transferable to in vivo studies. The results obtained in this study could help to lay the foundations for further levels of investigation into how gold nanoparticles behave in the body.

Lipid membranes, found in a continuous bilayer around all cells, act as a key barrier that keeps out or allows in selected ions, proteins, and other molecules when needed, and prevents the organelles of the cell from diffusing out. The study showed how the temperature and the charge of lipids in the membrane are clear factors that modulate the presence of energy barriers affecting the interaction of the nanoparticle with the membrane.

The lipid charge is highly relevant for biological systems as plasma membranes are inherently negatively charged: this is critical to the effectiveness of ion pumps that move charged atoms in and out of the cell, creating polarisation central to the primary function of many cells. Understanding how the molecular mechanisms are influenced by temperature can be valuable as they can indicate how the natural biological system may be affected by varying temperature fluctuations. This understanding can then be used to tune the system across the phase of the lipid bilayer in the experimental environment. The results demonstrate how the presence of charged lipids determines the fate of AuNP — whether it is adsorbed or internalised by the cell — and how the AuNP-interaction responds to temperature in the case of non-charged and negatively charged bilayers.

A computational approach

Using the computational technique of coarse-grained molecular dynamics (MD), the study shows how the lipid charge can affect the cooperative behaviour, or aggregation, of AuNPs. It was found that negatively charged lipid can favour the aggregation of nanoparticles, a cooperative effect that can be fatal for the membrane stability. Furthermore, different molecular mechanisms for nanoparticle-membrane interactions were revealed that explain how nanoparticles become internalised in the lipid membranes.

Neutron reflectometry was the chosen technique for this study. It provides a wealth of information on the structure of thin films and solid surfaces, and is particularly well suited to the study of interfaces between solids and liquids. The technique is highly versatile, able to examine a wide variety of materials. It is the perfect tool for examining the molecular details of the lipid/nanoparticle interaction, providing unambiguous insight into the behaviours of the molecular components.

Institut Laue-Langevin (ILL) is the world’s flagship neutron science facility, and provides the tools for scientists from across the globe and all scientific fields to further investigate the structures at the centre of their research. The D17 instrument at ILL is a horizontal scattering geometry designed for high flux and flexibility, it is one of the facility’s two reflectometers, and is well suited to the study of solid-liquid interfaces and membranes.

In addition to the neutron reflectometry data, the researchers implemented Molecular Dynamics (MD) — a computational simulation method for studying the movement of atoms — to demonstrate how gold nanoparticles interact within the system at the atomic level. It provides a complementary tool to interpret and explain the data obtained on real systems by neutron reflectometry. The study indicates the potential destructive effects of gold nanoparticles on the cell membrane, as well as how a combination of neutron scattering and computational methods provides researchers with a much better understanding of the mechanisms at play.

A bright future for the field

First contact between a nanoparticle and a living cell occurs through a biological membrane, so it is extremely important to understand what is governing the interaction with the plasma membrane.

However, real membranes are complex in terms of their structure, composition, and properties (for example, presence of several lipid types, cholesterol, membrane proteins, glycocalyx). It is difficult to establish models that can predict the fate of nanoparticles interacting with a real plasma membrane or outline the effect of the interaction on the membrane structure and stability. Instead, simpler models can be used to represent some essential membrane characteristics.

Computational and neutron techniques have together provided a clearer indication of what influences the behaviour of nanoparticles. This can help us predict how cells will interact with nanoparticles in future applications. Research into the possible mechanisms for implementing gold nanoparticles in medical applications such as drug delivery must be accompanied by a wealth of studies into where the high-potential properties could also have extensive yet unwanted effects.

It is also important to ensure we develop the tools to investigate further — to ensure nanoparticles can be applied both effectively and safely. Developments in neutron science techniques and advances in sample environment and preparation, performed at world-class facilities such as ILL, are helping us to reach this point.

* Giovanna Fragneto, Institut Laue-Langevin, 38042 Grenoble/France,

* * Marco Maccarini Université Grenoble Alpes

(ID:46074456)