Being able to perceive the environment is one of the most important features of an organism, over the course of evolution, many different senses have been developed, the most common of which, are shared by our species. Since organisms have been subjected to strong selective pressure, every little piece of information that can help orient them in the environment is precious. So, it's not surprising that organs and tissues capable of perceiving even the small geomagnetic force have been the subjects of evolution.

Being able to perceive the North and South direction is important since along this axis minor differences in microenvironments can be found. Differently from chemotaxis, magnetotaxis has the benefit of being unidirectional and may help the organism to move in the media having a fixed point of reference.

Here I explore a little into detail the molecular mechanism of magnetoreception, focusing in particular on magnetotactic bacteria (MTBs) and the evolution of magnetosomes.

The main principle of this strategy is to create an internal compass in the form of a metallic needle synthesized through the biomineralization of iron-rich substrates, forming either magnetite (Fe3O4) or greigite (Fe3S4).  These minerals are organized in aligned beads chains with different structures (see Pic1), with each unit ranging from 35 to 120 nm. Differently from other types of senses or taxis, magnetotaxis is passive, it doesn't induce a response from the host organism, which is passively oriented by the magnetosomes themselves [4].


Pic1: Different morphologies of magnetosomes (in black) in MTBs under electron microscope [7].

Evolution and distribution

The study of MTBs phylogeny has been a hot topic in the last few years, the characterization of the lineages has developed greatly going from two to sixteen different phyla over the span of 8 years. It has been proven that magnetotaxis has a monophyletic origin, evolving once in the history of life, by an ancestor probably being the first species capable of biomineralization too. The complexity of genes encoding for magnetosome-forming proteins suggests that in addition to the gene inheritance from higher taxa, a series of horizontal gene transfer events are involved in their evolution (plasmids).[2]

MTBs are widely spread in different water environments, with different depths, temperatures, and salinity levels, often in anaerobic or microaerobic conditions. Of these species, only a few can be grown in pure cultures, and the majority of studies use either Alphaproteobacteria Magnetospirillum magneticum or Magnetospirillum gryphiswaldense as models [4].

The most ancient samples of fossilized magnetosomes have been dated around 1.9 billion years ago, but the analysis of molecular clocks revealed that functional genes for the synthesis of magnetosomes could have been present 3 billion years ago. To better estimate the evolution of such old forms of life, it is important to consider the environmental conditions back then, in particular the quantity of oxygen, iron, sulfur, and the reducing potential. Their function could have changed during evolution, one possibility is that they used to be a simple mechanism of iron storage, or to regulate the oxidative potential in the cell, acquiring their function as organelles of perception only later. [2].

The evolution of magnetosomes and iron biomineralization requires a low level of oxygen, setting the origin of this trait before the Great Oxygenation Event (GOE), a period between 2.460 and 2.426 billion years ago when the bio-production of molecular oxygen started [4].


Metabolic pathways

Magnetosomes are formed by an organic bilayer membrane and an inorganic core formed by ferromagnetic minerals. These organelles are arranged in a chain fashion, to increase the magnetic dipole moment, the physical characteristics of magnetosomes are heavily controlled by genes and environmental conditions like pH, oxygen, iron content, and temperature [3,4].

Each step for magnetosomes synthesis is controlled by specific proteins referred to as Mam (Magnetosome Membrane) proteins, coded in a highly variable genetic island, for example in Magnetospirillum strains the Mam proteins are coded in 4 different operons. Magnetosome synthesis has 4 main steps:

  1. Invagination of bacterial membrane: a vesicle in the inner cytoplasmic membrane is formed, guided by environmental factors and Mam proteins, the vesicle can then remain attached to the cellular membrane or be released into the cytoplasm. 
  2. Uptake of iron: ferrous ions are accumulated in the vesicle either by specific channel transporters or by another mechanism that involves the collection of FeP granules.
  3. Nucleation and growth of magnetite: this requires a highly regulated oxidative pathway since a precise ratio of 1:2 between Fe2+ and Fe3+ ions is required. Magnetite formation requires alkaline pH and high iron content inside the empty magnetosomes, but concentrating and regulating the oxidative state of iron is not enough to create magnetite crystals. Heme-containing protein (MamT) and protein in the cytoskeleton seem to play an important role in getting the crystal growth to start.
  4. Chain arrangement: single magnetosomes are arranged in chain-like structures that vary a lot even between different strains. These chains are probably formed by Mam and actin-like proteins often found alongside magnetosome chains, building protein-protein interactions from the membranes around nanocrystals [5].

It's important to note that the transport and nucleation of iron are not completely separated steps, since in some models, soluble iron is first oxidized into a ferrihydrite precursor and then transported inside the new forming magnetosome, then inside the Mam, this precursor is partially reduced in forming magnetite. In other studies, iron from ferritin-like proteins and ferrous ions co-precipitate inside the magnetosomes to form the initial crystal. Other precursors could also be formed in the periplasmatic space and then introduced in the forming magnetosome during the invagination of the membrane [4].

The specific shape of the magnetosome subunit could be influenced by the presence of binding proteins (Mms6), the mechanism is still under study, but when these proteins were included in an in vitro reaction for the production of magnetite nanocrystals, a narrower distribution of sizes and shapes was found [5].


Pic2: Maximum likelihood phylogeny of MTBs [8].


Biotecnological applications

The regularity and wide range of crystal sizes and shapes found in magnetosome sub-units, offer a valid alternative to chemically synthesized magnetic nanoparticles. However, their synthesis is still limited by cytotoxicity. Another advantage is that magnetosomes are naturally covered by the Mam proteins, and charged groups on their surface would offer a connectivity point for active biomolecules.
Once purified, these particles can be used for drug delivery, system bioimaging, biomolecule extraction, and the construction of biosensors [3].

One interesting application of magnetosomes is in hyperthermia treatment, this is a technic used to cure cancer in which paramagnetic nanoparticles are delivered to the tumor cells, and once inside, heat is induced through a nearby alternating magnetic field. The heat produced this way will then kill the tumor, the problem in using chemically synthesized nanoparticles is the sub-optimal heating given by the small size and their tendency to aggregate. 
For this purpose, MTBs can be grown in a bioreactor using the dissolved oxygen as a triggering condition for the production of magnetosomes, for example by keeping it high to maximize biomass production first and then reducing it to trigger magnetosome formation. After the magnetosomes are produced, they're extracted using NaOH washings and sonication to separate them from the cell debris and obtain the single magnetic nanoparticles. Finally, proteases and other methods can be used to clean and remove even adsorbed proteins on the surface of the crystal.

The purified magnetosomes have been applied for hyperthermia only in proof-of-concept studies that had mice as subjects, in which particle suspensions were injected into the tumor. It was found that in general magnetosomes were more efficient than chemically synthesized nanoparticles, in terms of tumor elimination and reached temperature (45-46 °C). It was also found that chained magnetosomes were more efficient in the treatment, since less prone to aggregation  [6].

References:

  1. Wan, J., Monteil, C. L., Taoka, A., Ernie, G., Park, K., Amor, M., ... & Komeili, A. (2022). McaA and McaB control the dynamic positioning of a bacterial magnetic organelle. Nature Communications, 13(1), 5652.
  2. Goswami, P., He, K., Li, J., Pan, Y., Roberts, A. P., & Lin, W. (2022). Magnetotactic bacteria and magnetofossils: Ecology, evolution and environmental implications. npj Biofilms and Microbiomes, 8(1), 43.
  3. Jacob, J. J., & Suthindhiran, K. (2016). Magnetotactic bacteria and magnetosomes–Scope and challenges. Materials Science and Engineering: C, 68, 919-928.
  4. Strbak, O., Hnilicova, P., Gombos, J., Lokajova, A., & Kopcansky, P. (2022). Magnetotactic Bacteria: From Evolution to Biomineralization and Biomedical Applications. Minerals, 12(11), 1403.
  5. Komeili, A. (2012). Molecular mechanisms of compartmentalization and biomineralization in magnetotactic bacteria. FEMS microbiology reviews, 36(1), 232-255.
  6. Alphandéry, E., Chebbi, I., Guyot, F., & Durand-Dubief, M. (2013). Use of bacterial magnetosomes in the magnetic hyperthermia treatment of tumours: A review. International Journal of Hyperthermia, 29(8), 801-809.
  7. Shively, J. M., Cannon, G. C., Heinhorst, S., Fuerst, J. A., Bryant, D. A., Maupin-Furlow, J. A., ... & Federici, B. A. (2019). Intracellular structures of prokaryotes: Inclusions, compartments and assemblages. In Encyclopedia of microbiology (pp. 716-738). Elsevier.
  8. Lin, W., Zhang, W., Zhao, X., Roberts, A. P., Paterson, G. A., Bazylinski, D. A., & Pan, Y. (2018). Genomic expansion of magnetotactic bacteria reveals an early common origin of magnetotaxis with lineage-specific evolution. The ISME Journal, 12(6), 1508-1519.