When researchers study biological processes in cells, it helps if they have nanoscale sensors to take measurements. One approach is to carefully build and embed sensors into cells. (For an example with nitrogen–vacancy centers, see the 2020 PT story “Nanodiamonds shine as subcellular thermometers.”) Another option is to exploit the biological machinery that’s already there. Because of advances in genetic engineering, researchers can assemble protein sensors in situ by manipulating the proteins’ DNA. Now Gabriel Abrahams and Harrison Steel, both at the University of Oxford, and their colleagues have engineered a fluorescent and magneto-responsive protein that has boosted magnetic-sensing capabilities.
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The AsLOV2 protein, illustrated here, was used as a precursor to develop the MagLOV 2 protein through directed evolution. The parts of the AsLOV2 structure that were mutated to make MagLOV 2 are highlighted in blue and purple. MagLOV 2 is more sensitive to magnetic field effects than AsLOV2 and can be used as a quantum sensor.
Abrahams and colleagues started with a well-known and biocompatible fluorescent protein and engineered it to have magnetic-sensing properties.
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Then, using a technique called directed evolution, they mutated the protein, screened the resulting variants for the ones with the highest sensitivities to magnetic field strength, and then repeated the process several more times. (To read more about directed evolution, see the 2018 PT story “Chemistry Nobel winners harnessed evolution to teach old proteins new tricks.”)
The researchers found a protein, which they named MagLOV 2, that at room temperature in living cells exhibits optically detected magnetic resonance. By shining a laser on the protein, they could excite two electrons, which develop spins that are quantum mechanically linked. The protein’s fluorescence signal depends on what spin states the electrons are in. Because the spins are influenced by magnetic fields, a resonant RF field can, on demand, drive transitions between the spin states.
Abrahams and colleagues demonstrated that when the fluorescent MagLOV 2 is exposed to magnetic and RF fields, it can be used to measure the locations of proteins in cell cultures and of other structures embedded in a 3D volume. The protein sensor is less sensitive to light scattering by biological tissue than other fluorescence-based sensors, so it could outperform various localization techniques, such as fluorescence-modulated tomography.
Abrahams and colleagues also determined that in the presence of other magnetic chemical species, MagLOV 2 exhibits a decreased sensitivity to magnetic field effects. By quantifying the protein’s response to those effects, researchers could use the new quantum sensor to identify magnetic-signal-generating molecular species, such as free radicals and metalloproteins, which are critical in physiological processes such as cell signaling, immune responses, and metabolism.