Journal Article

27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells

Zhang, Xin, Yang, Zhenye, Ji, Xinmiao, Tian, Xiaofei, Li, Zhiyuan, Wang, Huizhen, Zhang, Lei, Mitchison, Timothy J, Hou, Yubin, Lu, Qingyou, Wang, Ze, Pi, Li, Yu, Fazhi

2017

Overview

Purified microtubules have been shown to align along the static magnetic field (SMF) in vitro because of their diamagnetic anisotropy. However, whether mitotic spindle in mammalian cells can be aligned by magnetic field has not been experimentally proved. In particular, the biological effects of SMF of above 20 T (Tesla) on mammalian cells have never been reported. Here we found that in both CNE-2Z and RPE1 human cells spindle orients in 27 T SMF. The direction of spindle alignment depended on the extent to which chromosomes were aligned to form a planar metaphase plate. Our results show that the magnetic torque acts on both microtubules and chromosomes, and the preferred direction of spindle alignment relative to the field depends more on chromosome alignment than microtubules. In addition, spindle morphology was also perturbed by 27 T SMF. This is the first reported study that investigated the mammalian cellular responses to ultra-high magnetic field of above 20 T. Our study not only found that ultra-high magnetic field can change the orientation and morphology of mitotic spindles, but also provided a tool to probe the role of spindle orientation and perturbation in developmental and cancer biology. Nowadays, a number of methods can be used to ‘look’ inside the body to investigate potential health problems. One of these is a technique called magnetic resonance imaging (MRI) that uses magnetic fields that are several hundred times stronger than a fridge magnet (or over 10,000 times stronger than the Earth’s natural magnetic field) to generate images of the inside of the body. In general, stronger magnetic fields enable higher quality images to be obtained. However, the effects of exposing the body’s cells to these magnetic fields have not been fully determined. Like most other biological materials, protein polymers called microtubules can respond to high magnetic fields – for example, by aligning with the field. Microtubules play a number of roles inside cells. This includes forming the mitotic spindle that separates copies of chromosomes – the structures in which the majority of a cell’s genetic material is stored – equally between dividing cells. The orientation of the mitotic spindle determines the direction in which a cell will divide. This direction is important for generating different types of cells and tissues. Furthermore, many cancerous cells have incorrectly oriented spindles. Zhang, Hou et al. have now exposed cancerous and normal human cells to magnetic fields of varying strengths. The maximum magnetic field strength tested (27 Tesla – or around 10 times the highest field strengths produced by standard hospital MRI scanners) did not kill the cells after four hours of exposure, but the orientation of the spindles inside the cells did change. In addition, the 27 Tesla magnetic field caused spindles that were perpendicular to the direction of the field to widen. At an intermediate field strength (9 Tesla – a magnetic field strength that has been used in some experimental MRI scanners), the orientation of the spindle only changed after three days of continuous exposure to the magnetic field. Lower field strengths (such as those currently used in hospital MRI scanners) did not alter the orientation of the spindle even after seven days of exposure. Zhang, Hou et al. also observed that the magnetic field acts on both the microtubules and chromosomes. However, the alignment of the chromosomes in the cell was the greatest determinant of the direction in which the spindle would align itself in response to the magnetic field. The next step is to analyze the consequences of magnetic field-induced spindle orientation changes – can these lead to cancer or reduce cancer growth, or change how animal tissues develop? Understanding how to control the position of the spindle could also ultimately make it possible to use ultra-high magnetic fields to engineer tissues or stimulate their regeneration.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Anisotropy / Apoptosis / Biophysics and Structural Biology / Cancer / Cell Biology / Cell cycle / Cell division / Cell Line / Chromosomes / Chromosomes, Human - radiation effects / Deoxyribonucleic acid / DNA / Flow cytometry / Health aspects / Humans / Laboratories / magnetic field / Magnetic Fields / Mammalian cells / Metaphase / microtubule / Microtubules / Mitosis - radiation effects / Morphology / Proteins / Software / Spindle (Cytoplasm) / Spindle Apparatus - radiation effects / spindle orientation / Spindles / Xenopus