The interactions that bind complex metal nanoparticles

For a long time, researchers have been investigating the unique properties of nanoparticles of pure gold coated with a thin layer of specific molecules. These particles may not only find applications as drug delivery devices, but they can also help investigate the behavior of matter at tiny scales.

However, the chemical properties that cause the aggregation of these nanoparticles have been debated. Now, NCCR Bio-Inspired Materials researchers at the University of Fribourg and EPFL revealed that different types of forces contribute to the attraction between nanoscale gold particles.

“If you want to use these nanoparticles as a therapeutic agent or a drug delivery system, you want to know how they interact with biological objects such as membranes and proteins,” says NCCR principal investigator Stefano Vanni, professor of biochemistry at the University of Fribourg, who led the study. “The more you know about them, the more you can improve their design for potential applications.” By looking at how these minuscule particles interact with each other, Vanni’s work contributes to the understanding of how they behave.

The particles, called “monolayer-protected gold nanoparticles”, are characterized by a metal core, typically measuring a few nanometers in diameter, covered by a layer of carbon-based materials that are responsible for the particles’ structure and function. As a result, the chemical properties of the nanoparticles can be modified by changing the composition of their outer shell.

However, so far there’s been little consensus on how chemical forces on the particles’ outer layer make them come together. To address this question, Vanni and his colleagues studied monolayer-protected gold nanoparticles using computer simulations that analyze the physical movements of atoms and molecules. Then, they combined the simulations with a powerful technique for imaging structures at the individual atom level.

Hydrophobic forces — which describe the attraction between water-hating molecules — are a source of aggregation for nanoparticles. But interactions between charged molecules, known as electrostatic interactions, can also bring two or more nanoparticles together, the researchers found.

When two nanoparticles get very close to each other, their aggregation is mainly driven by hydrophobic interactions. As the distance between the particles increases, they repel each other because they have the same charge. However, there is a “Goldilocks” distance between the particles at which a specific ratio of charge and hydrophobic forces make electrostatic interactions attractive. As a result, the particles come together, the researchers found.

“That happens because of the very specific orientation and arrangement of the molecules on the surface, so the nanoparticles get stuck in what is called a metastable state, which is driven by electrostatic interactions,” Vanni says.

The study also revealed that this “metastable” state is mediated by a specific type of charged molecules called monovalent ions. Previous studies have suggested that monovalent ions could mediate the interaction between nanoparticles. “We found strong evidence in support of that,” Vanni says.

His analysis also suggests that monovalent ions can help to stabilize or de-stabilize colloidal systems — mixtures in which very small particles of one substance are distributed evenly throughout another substance. Because hydrophobic and charged interactions play a key role in biology, the findings could help researchers better understand how proteins and other biopolymers form aggregates within cells.

The results indicate that not only the charge but also the orientation of molecules within nanoparticles is important to modulate their function. “For proteins, it depends on their three-dimensional structure, and for nanoparticles, it depends on the type of molecules used to build the particles,” Vanni says.

The study, published in the journal Nanoscale, stemmed from a collaborative effort between Vanni and NCCR principal investigator Francesco Stellacci at the École Polytechnique Fédérale de Lausanne, whose team carried out experiments to validate findings from the computer simulations. The NCCR was key for the collaboration with Stellacci, Vanni says. “We met twice a year through the NCCR — that’s how the project started, and we’re continuing to work together on this.”

Reference: Petretto, E.; Ong, Q.K.; Olgiati, F.; Mao, T.; Campomanes, P.; Stellacci, F.; Vanni. S. Monovalent ion-mediated charge–charge interactions drive aggregation of surface-functionalized gold nanoparticle, Nanoscale, 2022, 14, 15181–15192. https://doi.org/10.1039/D2NR02824G (open access)