Gold's well-known antibacterial properties are derived from mechanical stress it applies to cells, according to a study published in Advanced Materials, in which bacteria were exposed to nanoparticles of the precious metal and had their cell walls stretched beyond their breaking point.

Both gold and silver, which do not chemically react with biological processes, have been used as antibacterial agents since ancient times, and their nanoparticle forms are heavily investigated for medical uses. Gold nanoparticles of various shapes and sizes have been considered by scientists for applications such as medical imaging and detection, drug delivery and cancer treatment.

“There are numerous reports of bio-inert nanoparticles possessing antibacterial activity; however, a definitive mechanism of antibacterial action of these nanoparticles remains unclear,” said Elena Ivanova, the paper’s lead author and a professor of physics at RMIT University in Australia.

“Some research hypothesized that spiky nanomaterials would rip and tear bacteria, other research cited oxidative stress or nanoparticle uptake as the cause of antimicrobial action,” she said.

In the new study, an international research team led by Ivanova finally explained how gold nanoparticles kill microbes through purely physical processes. Its findings could contribute to the development of an antibacterial treatment that employs nanostructures, as bacteria globally develop resistance to antibiotic medicine.

The research team created gold nanoparticles about 100 nm wide — one-eighth the width of a human hair — that were either roughly spherical or star-shaped. The nanoparticles were added to samples of two common disease-causing bacteria, Pseudomonas aeruginosa and Staphylococcus aureus, and caused extensive stretching, bulging and outright rupturing and death in both species.

“The results of our experimental work and theoretical simulations showed that an attached layer of nanoparticles could apply sufficient mechanical tension to the cell wall of the bacteria that it ends up breaking seemingly by stretching, like a balloon that is squeezed from different points until it explodes,” said Denver Linklater, a postdoctoral research fellow at RMIT and co-author of the study.

Despite brandishing spikes, the star-shaped nanoparticles were less effective at popping cell membranes than the spherical ones, contradicting the researchers’ expectations. The spikes reduced “available contact area” between the nanoparticles and cells, which they said was important in determining antibacterial success.

The researchers confirmed that the antibacterial effects were purely mechanical by creating an artificial model of a cell membrane and exposing them to gold nanoparticles, which led to similar rupturing results. This aligns with previous findings that the size and shape of nanoparticles is more important to rupturing cell membranes than their chemical composition.

Ivanova and some of her coauthors previously discovered nanostructures in insect wings that inflict mechanical damage on bacteria, including in cicadas and dragonflies. The structures in both insects had microscopic spikes about 60 or 80 nm wide, and they killed bacteria on the surfaces by impaling them to the point of popping. 

Nanostructures of a wide range of materials have been shown to kill bacteria, such as copper, aluminum oxide, graphene and others, but how they do it may vary. For instance, the structures on some insect wings stab into bacterial membranes, while the gold nanoparticles stretch them apart from the outside.

The mechanical damage nanoparticles can do to bacteria is why many hope they can help solve the problem of antibiotic resistance, in which bacteria around the world are gradually evolving resistances to antibiotics used in treatments. According to the U.S. Centers for Disease Control and Prevention, there are more than 2.8 million antibiotic-resistant infections and more than 35,000 resulting deaths in the country each year.

Ivanova said her team is moving its investigations to much smaller nanoparticles of 1 to 5 nm, which can freely enter bacteria as well as their nuclei. As a result, some scientists believe ultra-small nanoparticles can be even more potent against bacteria than their larger counterparts.

The article, “Antibacterial Action of Nanoparticles by Lethal Stretching of Bacterial Cell Membranes,” was published Nov. 12 inAdvanced Materials. The authors of the study were Denver Linklater, Gary Bryant, Russell Crawford and Elena Ivanova, RMIT University; Vladimir Baulin, Rovira i Virgili University; Xavier Le Guével, Grenoble Alpes University; Jean-Baptiste Fleury, Saarland University, Eric Hanssen, University of Melbourne; The Hong Phong Nguyen, Ton Duc Thang University; Saulius Juodkazis, Swinburne University of Technology; and Paul Stoodley, The Ohio State University. The lead author was Elena Ivanova.