The ability to detect and respond to magnetic fields is not usually associated with living things. Yet some organisms, including some bacteria and various migratory animals, do respond to magnetic fields. In migratory animals like fish, birds, and turtles, this behavior involves small magnetic particles in the nervous system. However, how these particles form and what they are actually doing is not fully understood.
In a new study, published February 28 in the online, open-access journal PLoS Biology, Keiji Nishida and Pamela Silver of Harvard Medical School take a major step forward in understanding these processes by making yeast magnetic and then studying how this magnetization is regulated.
Dr. Silver's lab uses 'synthetic biology' to generate organisms that do things that they don't usually do; for example, manipulating bacteria to produce fuel. In this paper, they make yeast—an otherwise non-magnetic organism—magnetic.
"Magnetism exists throughout nature," explained Dr. Silver. "In particular there are magnetic bacteria and we wonder how these might have evolved." In addition, human nerve cells may also contain magnetic particles; iron deposits are seen in neurological disorders such as Alzheimer's. Yeast are a simpler system and more readily amenable to genetic manipulation, so making them magnetic also offered the opportunity to investigate the requirements for magnetization and how it is regulated—which not only provides significant new insights into how magnetization functions and is regulated in this system, but might also offer insights into how these particles form and what they are doing in diseases like Alzheimer's.
The researchers induced magnetization by first adding iron to the yeast cells' growth medium and then introducing the human ferritin proteins, which form a shell around iron and prevent it from being stored elsewhere in the cell. Ordinarily, yeast cells use an iron transporter to move excess iron to cellular storage containers called vacuoles; the researchers deleted the gene for this transporter to prevent this from happening, thus allowing iron to accumulate in the yeast cells.
"The yeast were magnetized by adding genes to increase their ability to sequester iron and by mutating other genes to increase their magnetic properties by altering their metabolism," said Dr. Silver. Although yeast with just the iron transporter deleted became magnetic, yeast that express the human ferritin gene in combination with this deletion displayed stronger magnetism. This suggests that magnetization does not rely on magnetic properties in normal yeast cells, but shows that it can be induced by manipulating the existing iron transport system or by introducing iron sequestering genes.
The researchers conducted further genetic experiments to determine which signaling pathways contributed to the induced magnetization. They identified a gene that controls the reduction-oxidation conditions of a cell—reduction-oxidation referring to chemical reactions in which atoms transfer electrons between one another—and that also induced the formation of iron-containing particles and magnetization of the cells.
The wider impact of this study is that it shows how magnetization might be induced in other non-magnetic organisms. Even cells without intrinsic magnetic properties might become magnetized through changes to existing pathways of iron storage and by altering regulation of reduction-oxidation conditions. These findings open up many new potential avenues for research, including the examination of how magnetic particles function in neurodegenerative diseases. In addition, magnetization is "contactless, remote, and permeable" —so it's one potential way to generate interactions between cells, for example, that might be useful for both bioengineering and therapy.
"There are several applications," said Dr. Silver about this approach. "In bioprocessing, the ability to separate a specific population of cells using magnets; using magnetism to organize cells in tissue engineering; and using magnetism as an input for therapeutic cells and to track cells by MRI," are just a few potential uses that she highlighted.
Funding: This work was funded by the Japan Society for Promotion of Science Postdoctoral Fellowship for Research Abroad to KN, the ONR Multi Disciplenary Research Initiative (MURI) N00014-11-1-0725 and The Wyss Institute of Biologically Inspired Engineering. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Citation: Nishida K, Silver PA (2012) Induction of Biogenic Magnetization and Redox Control by a Component of the Target of Rapamycin Complex 1 Signaling Pathway. PLoS Biol 10(2): e1001269. doi:10.1371/journal.pbio.1001269
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