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

// Lei Zhang 1, * , Jihao Wang 1, 2, * , HongLei Wang 3, * , Wenchao Wang 1 , Zhiyuan Li 1 , Juanjuan Liu 1 , Xingxing Yang 1 , Xinmiao Ji 1 , Yan Luo 1 , Chen Hu 1 , Yubin Hou 1 , Qianqian He 1 , Jun Fang 1 , Junfeng Wang 1 , Qingsong Liu 1 , Guohui Li 3 , Qingyou Lu 1, 2, 4 , Xin Zhang 1 1 High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei, Anhui 230026, China 2 Hefei National Laboratory for Physical Sciences at The Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China 3 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 4 Collaborative Innovation Center of Advanced Microstructure, Nanjing University, Nanjing, Jiangsu 210093, China * These authors have contributed equally to this work Correspondence to: Xin Zhang, email: xinzhang@hmfl.ac.cn Qingyou Lu, email: qxl@ustc.edu.cn Guohui Li, email: ghli@dicp.ac.cn Keywords: EGFR, magnetic field, STM, cancer Received: March 09, 2016      Accepted: April 27, 2016      Published: May 19, 2016 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.