title: 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.
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.|Hefei National Laboratory for Physical Sciences at The Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Jihao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: HongLei
authors.initials: H
authors.lastname: Wang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Wang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Liu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Yang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xinmiao
authors.initials: X
authors.lastname: Ji
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Hou
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: He
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Li
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.|Hefei National Laboratory for Physical Sciences at The Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China.|Collaborative Innovation Center of Advanced Microstructure, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Lu
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation / Q000235:genetics / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D066246:ErbB Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D045325:HCT116 Cells; D006801:Humans; D060526:Magnetic Fields; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000072417:Protein Domains / Q000235:genetics / Q000528:radiation effects; D014162:Transfection
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; STM; cancer; magnetic field