Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation

Abstract

Static magnetic fields (SMFs) can affect cell proliferation in a cell-type and intensity-dependent way but the mechanism remains unclear. At the same time, although the diamagnetic anisotropy of proteins has been proposed decades ago, the behavior of isolated proteins in magnetic fields has not been directly observed. Here we show that SMFs can affect isolated proteins at the single molecular level in an intensity-dependent manner. We found that Epidermal Growth Factor Receptor (EGFR), a protein that is overexpressed and highly activated in multiple cancers, can be directly inhibited by SMFs. Using Liquid-phase Scanning Tunneling Microscopy (STM) to examine pure EGFR kinase domain proteins at the single molecule level in solution, we observed orientation changes of these proteins in response to SMFs. This may interrupt inter-molecular interactions between EGFR monomers, which are critical for their activation. In molecular dynamics (MD) simulations, 1-9T SMFs caused increased probability of EGFR in parallel with the magnetic field direction in an intensity-dependent manner. A superconducting ultrastrong 9T magnet reduced proliferation of CHO-EGFR cells (Chinese Hamster Ovary cells with EGFR overexpression) and EGFR-expressing cancer cell lines by ~35%, but minimally affected CHO cells. We predict that similar effects of magnetic fields can also be applied to some other proteins such as ion channels. Our paper will help clarify some dilemmas in this field and encourage further investigations in order to achieve a better understanding of the biological effects of SMFs.

Cellular ATP levels are affected by moderate and strong static magnetic fields

“…For 9 T SMF, which is relevant to the 9.4 T MRI at periclinal stage, the decreased cellular ATP levels should also cause some caution. On the other hand, this might be a potential way to inhibit cancer cell proliferation, which is consistent with our previous findings that 9 T SMF could inhibit some human cancer cell proliferation [Zhang et al, ]. However, our previous results also show that 1 T SMF could inhibit multiple cancer cell proliferation [Zhang et al, , , ], which apparently cannot be explained by the increased ATP levels induced by 1 T in this study.…”

Cell type- and density-dependent effect of 1 T static magnetic field on cell proliferation

“…NIH-3T3 cells have been reported to be affected by 7-17 T SMFs [15] but CHO cells were shown to be irresponsive to SMFs ranging from moderate intensity SMFs to 13 T ultra-high SMFs in both ours and other people's studies [4, 7, 8]. Here we found that at high density, 1 T SMF reduced NIH-3T3 cell number but has minimal effects on CHO cells (Figure 4), which is consistent with previous reports.…”

“…We made a CHO cell line that stably overexpresses EGFR with a FLAG tag (CHO-EGFR cells) [4]. Here we examined them for their responses to 1 T SMF at different cell densities.…”

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

“…We found that 4 hr of exposure does not increase the non-lateral spindles (Figure 4B; Figure 4—source data 1) as 27 T SMF. We also tested 9 T SMF provided by a superconducting magnet (Zhang et al, 2016) and found that 4 hr of 9 T exposure does not increase the non-lateral spindles either (Figure 4C; Figure 4—source data 2). However, although exposure for a prolonged time of 3 days to 0.05 T or 1 T SMFs still had no effect (Figure 4D; Figure 4—source data 3), 9 T SMF treatment for 3 days could perturb spindle orientation (Figure 4E; Figure 4—source data 4).…”