Fyzikální ústav Akademie věd ČR

Cell Biology - Magnetic Control of Living Cell Machinery

The influence of spatially modulated high-gradient magnetic fields on human leukemia cells behavior is second line of research. We demonstrate that exploiting high-gradient micro-magnet arrays induces swelling and apoptosis of THP-1 cells as well as inhibits cell proliferation in the absence of chemical or biological agents. Under a prolonged exposure to a high-gradient magnetic field THP-1 cells were observed to swell up to 90% in volume. Mechanical stress raising due to the magnetic gradient forces exerted on a cell is shown to be responsible for triggering of cell swelling, formation of reactive oxygen species followed by apoptosis [1]. Such a magnetically controlled cell swelling could be also used to manipulate cell-to-cell communication which is affected by the extracellular space volume as well as cell size.
To manipulate stem cells by magnetic field submicron-patterned NdFeB films were developed. The micromagnet arrays produce magnetic fields (fig. 6) which affect the cells’ life as: causing the cell migration and adherence to a magnetic pillar [2]. The underlying mechanisms which incorporate the both physical and biological factors affecting cells life were suggested. The building up of tunable interconnected stem cell networks is a challenging perspective for tissue engineering and regenerative medicine.
The discovered cell patterning has a great application potential. Manipulating the fate and spatial organization of stem cells and the creation of an interconnected cell network with externally applied magnetic fields opens exciting perspectives for tissue engineering and regenerative medicine. Nowadays, the focus in medicine on molecular genetics has resulted in a disregard for the physical basis of treatment even though many diseases originate from changes in cellular mechanics. Here, we show that oscillating high-gradient magnetic field (HGMF) and mechanical vibration affect adipogenic differentiation of mesenchymal stem cells by the transmission of mechanical stress to the cell cytoskeleton, resulting in F-actin remodeling and subsequent down-regulation of adipogenic genes [3]. Our results showed that low-frequency oscillating HGMF and mechanical vibration reduced the adipogenic differentiation of MSCs.

             

(a) Scheme of the oscillating HGMF experimental setup.
(b) Modulus of magnetic field gradient, calculated at the distance 0.2 mm from the magnet pole.
(c) Confocal fluorescence analysis of cytoskeleton organization of the cell treated with HGMF.
(d) Detection of changes in DNA organization upon oscillating HGMF exposure for 5 days, as assessed
by “comet assay.” Nucleoids with low (asterisk) and high level of DNA damage; arrows show disorganized structure of intact DNA in the “head of comet.”
(e) Calculated vector field of the magnetic gradient, above a cylindrical magnet with the diameter
and length of 1 mm.

References
1. V. Zablotskii, et al., Modulation of monocytic leukemia cell function and survival by high gradient magnetic fields and mathematical modeling studies. Biomaterials (2014) 35: 3164.
2. V. Zablotskii, et al., Life on magnets: stem cell networking on micro-magnet arrays. PLoS One (2013) 8: e70416.
3. V. Zablotskii, et al., Down-regulation of adipogenesis of mesenchymal stem cells by oscillating high-gradient magnetic fields and mechanical vibration. Appl. Phys. Lett. (2014) 105: 103702.  

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