Magnetogenetics

Magnetogenetics is the remote activation of cells using magnetic fields.

Magnetogenetics is related to optogenetics, which is the manipulation of cell behavior using light. Magnetogenetics instead use magnetic stimuli to manipulate cell behavior, which can be less invasive in sensitive tissues, like neural tissue, since magnetogenetic methods do not require invasive surgery.[1] This field developed from combining principles observed in various magnetotactic bacteria with optogenetic techniques,[2] helping researchers manipulate cell behaviors and gene expression in the presence of magnetic fields. There are multiple tissues in the body that can be combined with magnetic proteins or with magnetosomes from bacteria, including brain tissue, tumors, and others. The activation of the magnetic compounds can cause effects on the organism via either mechanical or thermal effects.

Magnetotactic bacteria

Magnetotactic bacteria (MTB), which are utilized for the applications of magnetogenetics, are typically found in aquatic environments and uniquely contain an organelle called a magnetosome. Microbes used to be thought as randomly spaced throughout an environment, research has been showing that magnetism of the earth and nearby magnet field may impact the locations of microbes.[3] Now there is a significant amount of data found that can correlate the magnetic fields of objects and the earth, there is still more data required in order to make this correlation connected to causation.[3] This membraned organelle contains a microscopic crystalline structure of a magnetic iron mineral. Magnetosomes are organized in long, chains which assists in the cells motile ability to align and swim parallel to magnetic fields, known as magnetotaxis[4]These orientations caused by the magnetosome can have various implications on eukaryotic cells that they inhabit. Two magnetotactc bacteria commonly used in laboratory settings are Magnetospirillum megneticum (AMB-1) and Magnetosprillium gryphiswaldense (MSR-1) due their ease in cultivation and ability to produce the compounds necessary for crystalline structure formation. To synthesize the magnetosomes first the cell invaginates it outer membrane to create a vesicle and allows for the magnetosome proteins to be sorted in the vesicle membrane. Iron is the imported into the magnetosome as crystal-coated structures, and the magnetosomes aggregate as a chain[5]

Mechanisms

Brain stimulation

In the presence of a magnetic field, paramagnetic proteins either thermally or mechanically open ion channels in a neuron, facilitating free movement of compatible ions, and activating the neuron.

Magnetogenetic techniques involve first fusing TRPV class receptors, which are selective calcium transporters, with a paramagnetic protein (typically ferratin).[6][7] These paramagnetic proteins, which typically contain iron or have iron-containing cofactors, are then stimulated with a magnetic field exerted on the brain. The next steps in the activation of the neurons is still unclear, but it is thought that the ion channels are activated and opened either by a mechanical force exerted by the paramagnetic proteins,[2] or by the heating of these proteins in response to the stimulation by the magnetic field.

Cancer

Magnetosomes can be engulfed by certain eukaryotic cells, and this allows the eukaryotic cells to be manipulated in specific ways. One such application is using magnetic resonance imaging (MRI). The paramagnetic particles contained within the magnetosomes in these bacteria can be used to positive or negative contrast agents.[8] Magnetotactic bacteria have been found to be preferentially taken up by tumor cells allowing for these tumors to be imaged in an MRI.[9]

Magnetic hyperthermia is another potential application of the magnetosomes produced by these bacteria. Hyperthermia therapy is a current clinical technique used to treat cancers; however, magnetic hyperthermia could offer a more specific targeted cancer treatment.[9]

References

1. Nimpf S, Keays DA (June 2017). "Is magnetogenetics the new optogenetics?". The EMBO Journal. 36 (12): 1643–1646. doi:10.15252/embj.201797177. PMC 5470037. PMID 28536151.
2. Vogt N (2016-10-31). "Biophysics: Unraveling magnetogenetics". Nature Methods. 13: 900–901. doi:10.1038/nmeth.4060. ISSN 1548-7105.
3. Lin, Wei; Bazylinski, Dennis A.; Xiao, Tian; Wu, Long-Fei; Pan, Yongxin (2014). "Life with compass: diversity and biogeography of magnetotactic bacteria". Environmental Microbiology. 16 (9): 2646–2658. doi:10.1111/1462-2920.12313. ISSN 1462-2920.
4. Lefèvre CT, Bazylinski DA (September 2013). "Ecology, diversity, and evolution of magnetotactic bacteria". Microbiology and Molecular Biology Reviews. 77 (3): 497–526. doi:10.1128/MMBR.00021-13. PMC 3811606. PMID 24006473.
5. Uebe R, Schüler D (September 2016). "Magnetosome biogenesis in magnetotactic bacteria". Nature Reviews. Microbiology. 14 (10): 621–37. doi:10.1038/nrmicro.2016.99. PMID 27620945.
6. Long X, Ye J, Zhao D, Zhang SJ. "Magnetogenetics: remote non-invasive magnetic activation of neuronal activity with a magnetoreceptor". Science Bulletin. 60: 2107–2119. doi:10.1007/s11434-015-0902-0. PMC 4692962. PMID 26740890.
7. Wheeler MA, Smith CJ, Ottolini M, Barker BS, Purohit AM, Grippo RM, Gaykema RP, Spano AJ, Beenhakker MP, Kucenas S, Patel MK, Deppmann CD, Güler AD (May 2016). "Genetically targeted magnetic control of the nervous system". Nature Neuroscience. 19 (5): 756–761. doi:10.1038/nn.4265. PMC 4846560. PMID 26950006.
8. Alphandéry E (2014). "Applications of magnetosomes synthesized by magnetotactic bacteria in medicine". Frontiers in Bioengineering and Biotechnology. 2: 5. doi:10.3389/fbioe.2014.00005. PMC 4126476. PMID 25152880.
9. Benoit MR, Mayer D, Barak Y, Chen IY, Hu W, Cheng Z, Wang SX, Spielman DM, Gambhir SS, Matin A (August 2009). "Visualizing implanted tumors in mice with magnetic resonance imaging using magnetotactic bacteria". Clinical Cancer Research. 15 (16): 5170–7. doi:10.1158/1078-0432.CCR-08-3206. PMC 3409839. PMID 19671860.