Genetically Encoded Magnetometer for Intracellular Dynamic Measurement

PROJECT SUMMARY
Mounting evidence suggests that magnetic fields may modulate important functions in cells. For example,
magnetic fields can influence the spin state of photo-generated radical pairs in many flavoproteins, determining
the rate of downstream reactions that govern cellular behaviors including circadian rhythms, DNA repair, and
navigation of migratory birds. However, only low-to-moderate efficacy has been reported in clinical applications
such as transcranial magnetic stimulation (TMS) and magnetotherapy, to treat epilepsy, depression and chronic
pain. Improvement in treatment efficacy has been long stalled because the underlying molecular mechanism is
poorly understood. This lack of progress is mostly due to not knowing the molecular mechanism of magnetic
modulation. To measure the effective intracellular magnetic field to which biomolecules are exposed is the first
step of building such understanding. The intracellular magnetic field is likely heterogeneous and not equivalent
to the externally applied field of TMS or magnetotherapy, due to heterogeneous cellular compositions with
varying magnetic permeabilities, as well as the heterogenous dynamic magnetic fields resulting from ion fluxes
through ion channels.
Currently no appropriate magnetometer exists to map the heterogeneous intracellular magnetic fields, though
cellular measurement has been attempted using nitrogen a vacancy-center nanodiamond-based magnetometer,
which can only provide sparse spatial readouts across the cell. Moreover, the necessity of subjecting cells to
microwave radiation during nitrogen vacancy-center nanodiamond-based magnetometry is potentially harmful to
cells. Herein we propose a genetically encoded magnetometer (GEM). GEM is a recombinant protein the
backbone of which is a modified version of magnetosensitive flavoprotein. We will demonstrate that the
heterogenous intracellular magnetic field can be mapped by expressing GEM in cells at unprecedented spatial
resolution without the use of microwaves. If successful, GEM will enable the mechanistic study of TMS and
magnetotherapy. In addition, it may also aid the evaluation of biological impacts due to pervasive presence of
devices emitting electromagnetic waves.

Grant Number: 5R21GM154219-02
NIH Institute/Center: NIH
Principal Investigator: Yun Chen