Nature's Living Magnets: An unexpected tool to treat disease

by Saman Hussain
figures by Daniel Utter

All living organisms have developed ways to move to places that are beneficial for them. Even tiny organisms like bacteria need to move towards food sources. Finding food becomes much easier if information from the environment is used to help in the search. For example, if you are looking for free pizza in your workplace, relying on randomly walking around and hoping to run into pizza will probably not work. However, if you use sensory cues such as the smell of pizza, the sight of a pizza box or a sign that says “free pizza,” you will probably find it faster. Similarly, bacteria have developed simple and efficient ways to move to desirable locations using their own “senses.” It is well known that different species of bacteria are able to swim towards food, towards light and away from toxic substances, all of which promote their growth and survival. One of the lesser known and understood forms of bacterial movement is a process called magnetotaxis, by which certain species of bacteria are able to orient themselves along magnetic fields and move towards the North or South pole.

Scientists have been working to understand how magnetotactic bacteria (MTB) can sense magnetic fields, hoping to harness this ability for a variety of uses including nanoparticle research and even medical treatments. Over the years, they have discovered many new details about how and why bacteria carry out magnetotaxis, which make this behavior even more remarkable than originally thought.

Why carry out magnetotaxis?

Imagine living in a world where oxygen only exists in one spot. In such a world, we would spend all our resources figuring out where that spot is. Those among us who are able to find that spot fast will have a huge advantage over others. Bacteria that exhibit magnetotaxis tend to live in extreme environments, and most require little to no oxygen to survive. For instance, regions of low oxygen occur deep in water bodies, and bacteria that can reach this spot have a much greater chance of surviving. Thus, to navigate our mostly oxygenated world, MTB need a way to find the place in the ocean with the optimal oxygen content.

Since the magnetic field of the Earth is oriented almost vertically in most parts of the Earth, MTB align themselves to the magnetic field and migrate to regions of low oxygen faster and more easily than those bacteria swimming randomly in all directions. MTB existing in the Northern hemisphere are North pole-seeking and MTB in the Southern hemisphere are South pole-seeking. Hence, both types migrate towards the bottom of water bodies in their respective hemisphere (Figure 1A).

Once MTB align to the Earth’s magnetic field, they still need to decide whether to move forwards or backwards. The situation is similar to a railway track, which provides a line along which trains move, but the train can move in both directions along the track. By comparing the oxygen concentration over time as they swim, MTB decide whether to move forwards or backwards along the magnetic field. If the oxygen concentration is too high in their current location, they rotate their flagella (hair-like appendages that rotate to help bacteria swim) clockwise to move forward as this will propel them deeper into the ocean towards lower oxygen concentrations. Similarly, if the oxygen concentration becomes too low, they switch to rotating their flagella counter-clockwise to move backwards towards higher oxygen concentrations (Figure 1B).

Figure 1 A. Magnetotactic bacteria can move to the bottom of water bodies by aligning to the Earth’s magnetic field and moving forwards. B. Some magnetotactic bacteria localize to the optimal oxygen concentration by moving forwards when oxygen concentration is too high and backwards if it is too low.
Figure 1. A. Magnetotactic bacteria can move to the bottom of water bodies by aligning to the Earth’s magnetic field and moving forwards. B. Some magnetotactic bacteria localize to the optimal oxygen concentration by moving forwards when oxygen concentration is too high and backwards if it is too low.

In recent years, scientists have found that, due to this useful skill, MTB are quite common in nature. They live in widespread geographical locations, span many branches of the bacterial family tree and come in a variety of cell shapes. This diversity is evidence that magnetotaxis is extremely useful in nature: many different bacteria have managed to acquire this ability to meet their needs in different environments.

How can MTB sense magnetic fields?

To sense the Earth’s magnetic field, MTB use tiny magnets inside them called magnetosomes. These are essentially crystals of magnetic materials, primarily magnetite or greigite, bound by membranes. Instead of absorbing preformed crystals from the environment, MTB form these crystals inside themselves by pumping iron ions in from the environment (Figure 2).

Figure 2 Magnetotactic bacteria form magnetosomes by pumping iron ions into membrane compartments and forming crystals. Once formed, the magnetosome is fixed into a chain.
Figure 2. Magnetotactic bacteria form magnetosomes by pumping iron ions into membrane compartments and forming crystals. Once formed, the magnetosome is fixed into a chain.

Under the microscope, magnetosomes appear small and dark, and have a variety of particle shapes, ranging from circular to elongated and even bullet-shaped (a shape that does not exist naturally in crystals). The size of these tiny magnets is strictly controlled and is optimal to produce the maximum magnetic moment (the property which determines the strength and the direction of the north and south pole of a magnet), while keeping the minimum crystal size.

MTB contain chains of linearly arranged magnetosomes, since a single magnetosome cannot produce enough force to align the bacterial cell to an external magnetic field.

Magnetosomes as nanoparticles – an active area of research

Magnetic nanoparticles (tiny magnetic particles 1-1000nm in size) are used in many different areas of research. They are synthesized in industry and have a variety of uses such as catalyzing chemical reactions, wastewater cleaning and applying tiny amounts of force to push and pull on microscopic objects. Furthermore, scientists are also testing the potential of magnetic nanoparticles in medicine for uses such as cancer detection and treatment, treating infections and drug delivery to specific cells in the body.

Since the discovery of magnetosomes, active research is being done to harvest them from MTB in large quantities, as they are essentially pre-made magnetic nanoparticles. Industrially constructing nanoparticles of this size accurately and reproducibly is both expensive and difficult, making the idea of harvesting particularly appealing.

Magnetosomes are also being used to induce magnetic hyperthermia (using magnets to heat up cells that have taken up magnetosomes). Scientists have been able to kill pathogenic bacterial cells of Staphylococcus aureus, a common cause of infections, by pumping them full of magnetosomes and applying magnetic heat. Magnetic hyperthermia is also being explored in cancer research, as it can target and kill tumor cells (Figure 3). These therapies may prove particularly useful because they target only those cells that have taken up magnetosomes, leaving surrounding cells intact.

Figure 3 Magnetic nanoparticles in theoretical cancer treatment. A. Magnetic nanoparticles are coated with antibodies that recognize tumor cells. B. The nanoparticles are injected in a patient and they bind to the tumor. C. Applying changing magnetic fields heats up the nanoparticles and attached tumor cells. D. Tumor cells die.
Figure 3. Magnetic nanoparticles in theoretical cancer treatment. A. Magnetic nanoparticles are coated with antibodies that recognize tumor cells. B. The nanoparticles are injected in a patient and they bind to the tumor. C. Applying changing magnetic fields heats up the nanoparticles and attached tumor cells. D. Tumor cells die.

MTB have once again shown us how even single-celled organisms use all sorts of environmental signals to find ideal places for themselves. These tiny magnetic compasses of nature have come up with a unique solution to promote their survival and growth. What’s more, studying MTB and utilizing their strategies may ultimately have strong and lasting effects on environmental pursuits and the treatment of disease.

Saman Hussain is a fourth year graduate student in the Molecules, Cells and Organisms Biology program at Harvard University.

For more information:

An overview of magnetotactic bacteria: http://www.nature.com/scitable/knowledge/library/bacteria-that-synthesize-nano-sized-compasses-to-15669190

Information about the different mechanisms of magnetotaxis and different types of magnetosomes: http://www.calpoly.edu/~rfrankel/magbac101.html

A scientific review article summarizing the main studies done on MTB and their major findings: Faivre, Damien, and Dirk Schüler. 2008. “Magnetotactic Bacteria and Magnetosomes.” Chemical Reviews 108 (11): 4875–98. doi:10.1021/cr078258w.  http://www.cup.lmu.de/ac/kluefers/homepage/L/biominerals/magnetite_2008.pdf

A detailed description of the size-dependent magnetic properties of materials: http://www.irm.umn.edu/hg2m/hg2m_d/hg2m_d.html

 

Cover image from Nature. This shows an electron microscope picture of magnetotactic bacteria. The dark spots are the nanoparticles.