The nanotech of the magnetosome

When it comes to the understanding of the nanoscience behind some deeply mysterious magnetic microbes, neutrons are vital says Dirk Honecker…  

Perhaps one of the lesser-known processes that occurs on our planet, the iron-cycle is a vital and complex combination of pathways that moves the element iron through different states and environments.

The system has a number of biological players as well as chemical components. These organisms are crucially involved in the cycle, but can exploit it for their own means, often acquiring unusual properties.

One such group of organisms are the microbes called magnetotactic bacteria (MTB). These single-celled microorganisms take up iron from their aquatic surroundings, which may be freshwater such as lakes and ponds, or marine environments such as the ocean floor. Because these organisms flourish in low-oxygen environments, it is thought that these microbes may be similar to some of Earth's earliest inhabitants.

 Magnetosomes are membrane-bound structures within the cell, containing magnetic nanoparticles that the bacteria create by mineralising iron crystals from their environment  

They have long been of interest to researchers because of the fascinating ability they have acquired through the uptake of iron. They can form chains of magnetic particles that act as an internal compass. These nanoparticles, known as magnetosomes, provide the unique capabilities of the magnetotactic bacteria to orient themselves using the earth’s magnetic fields.

A range of other species are believed to have this sense for magnetic fields, known as magnetoreception, including sharks and stingrays, a number of mollusks and worms, some amphibians such as salamanders and turtles, homing pigeons, and even some mammals like deer and cattle. However, the possible mechanisms in these larger species have not been established. Magnetotactic bacteria provide the greatest opportunity for us to learn exactly how sensitive living organisms can be to the earth’s magnetism.

Miniature compass Magnetosomes are membrane-bound structures within the cell, containing magnetic nanoparticles that the bacteria create by mineralising iron crystals from their environment within their cells. The magnetosomes arrange into a chain that can sense the Earth’s magnetic fields, allowing the bacteria to move passively towards the riverbeds they inhabit.

Researchers have been exploring the potential applications of this internal compass for decades. The properties of MTB could be harnessed in future technologies such as drug-delivery systems, or medical nanorobots. However, some mystery persists as to exactly how the magnetosome compass operates. To be implemented in medical treatments, the nanoparticles must be entirely predictable and controllable, so we need to establish precisely how the mechanism works to potentially open the doors to exciting applications. These unusual nanoparticles have been examined with neutron beams to discover the underlying mechanisms that determine the configuration and geometry of the chains.

Analysing the arrangement 

[caption id="attachment_77500" align="alignleft" width="226"] TEM image of Magnetospirillum gryphiswaldense. Credit: Lourdes Marcano, UPV/EHU.[/caption]

Neutron scattering is a powerful method for revealing the minute details of substances down to individual atoms. In an international collaboration, researchers from University of the Basque Countries, University of Cantabria and the Institut Laue Langevin (ILL), set out to elucidate the precise structural configuration of the magnetosomes in a specific MTB strain called Magnetospirillum gryphiswaldense. The bacteria biomineralises Fe3+, the ferric ion, into magnetite (Fe3O4) – cuboctahedral shaped, single domain nanoparticles with a narrow size range of around 45 nm that are surrounded by a lipid bilayer membrane containing a set of proteins.

The specific technique the scientists utilised was small angle neutron scattering (SANS), which allowed them to see the magnetic microstructure of the organisms in detail in aqueous solution. The ILL’s D33 instrument was employed because of its polarised neutron beam mode, which allowed the researchers to analyse both the structural components and magnetic arrangement – possible because neutrons will interact with both. The magnetic structures within and in between nanoparticles are challenging to probe directly. Neutron-spin resolved (or ‘polarised’) small-angle neutron scattering is one of the few tools that can be used to investigate nanoparticles in the relevant scale.

Using SANS, the researchers managed to gain new insight into the structure of the magnetosome chain. This had previously observed to be bent, rather than straight, yet neutron probing has helped to explore what is happening further. As it turns out, the bends do not affect the direction of the net magnetic moment, but do cause the individual nanoparticle magnetic moment to deviate by 20 degrees from the chain axis. Once the deviation is taken into account, the interplay of the magnetic dipolar interactions between the nanoparticles, and the active assembly mechanism implemented by the bacterial proteins, explains the conformation of the chains in a helical-like shape: it is simply the lowest energy arrangement for the magnetic nanoparticles.

Applications?

These findings, published in Nanoscale, facilitate a better understanding of how the chain behaviour might affect applications of MTB. The magnetosome chain of the bacteria could provide directional motion within the steering system. The new understanding could guide the development of some revolutionary uses for the bacteria or magnetosomes alone.

Some of these uses, summarised in Molecules, would have a major impact on the medical field. By controlling the MTB or magnetosomes with an external magnetic source, we could enable them to deliver drugs to precise locations in the body. By releasing substances at the exact point where they are needed, these would minimise the unwanted effects of drugs in other parts of the body: side effects are a huge issue in medicine, with potentially lethal consequences.

This could be especially effective as magnetosomes alone are a relatively neutral and safe foreign agent to put into a patient. The shape, size and composition of the magnetosomes depends on the MTB species and the magnetic properties can be further tailored by incorporating other transition metals. The proteins present in the magnetosome membrane can be linked to bioactive molecules, making the magnetosomes biocompatible. The particles cannot replicate, cause infection, and are unlikely to produce a severe immune response because they lack the endotoxins that whole bacteria would have on their outer surface, which can activate responses from the immune system. Magnetosomes hold great potential for hyperthermia applications. As treatment against cancer, the heat produced by magnetic nanoparticles under an alternating magnetic field promotes cancer cell death without affecting the healthy ones.

These bacteria are central to many further applications, ranging from biomedical diagnostics, data storage, detection of food pathogens and even as medical ‘microrobots’ that perform minor procedures in the body. Nanorobots would enable minimally invasive medical procedures to be carried out, relieving patients of much of the trauma caused by current intrusive surgical methods. In this case, the precise conformation of the chain would be critical for it to function correctly and navigate around the body.

Similarly, with all of the potential applications of MTB and their nanoparticles, understanding the exact mechanism of the internal compass is essential for their development, and eventually their safe and effective use in the human body. Using neutrons has allowed us to take significant steps in completing our understanding of these unique microbes, but as with any potential medical innovation, it must be a predictable system, with far more research to go before these nanorobots start to operate in hospitals.

Author:

Dirk Honecker is D33 Instrument Scientist at the Institut Laue-Langevin. The ILL is the world’s flagship centre for neutron science managed by France, Germany and the United Kingdom, in partnership with 10 other European countries.