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A new class of biomolecules called magneto-sensitive fluorescent proteins, or MFPs, could improve imaging of biological processes inside living cells and potentially underpin innovative therapies.
The fluorescent proteins commonly used in biological studies respond solely to light being shone at them. But because that light gets scattered by tissues there are inaccuracies in determining exactly where the resulting fluorescence originates. By contrast, the MFPs created by a team led by Harrison Steel, head of the Engineered Biotechnology Research Group at the University of Oxford in the UK, fluoresce partly in response to highly predictable magnetic fields and radio waves that pass through biological tissues without deflection.
To detect where MFPs are located within living cells, the researchers apply both a static magnetic field with a precisely known gradient and a radiofrequency (RF) signal, which modulate the fluorescence triggered via excitation by a light-emitting diode (LED).
The emitted fluorescence is brightest whenever the RF is in resonance with a transition energy of the entangled electron system present within the MFP. Since the resonance frequency depends on the surrounding magnetic field strength, the brightness reveals the protein’s location.
As detailed in their recent Nature paper, the researchers engineered the MFPs by “directed evolution”: starting with a DNA sequence, making two to three thousand variants of it, and selecting the variants with the best fluorescence response to magnetic fields before repeating the entire process multiple times. The resulting proteins were tested via ODMR (optically detected magnetic resonance) and MFE (magnetic-field effect) experiments, revealing that they could be detected in single living cells and sense their local microenvironment.
Importantly, these MFPs can be made in research labs using a straightforward biological technique. “This is a totally different way of coming up with new quantum materials compared to other engineering efforts for quantum sensors like nitrogen vacancies [in diamonds] which need to be manufactured in highly specialized facilities,” explains first author Gabriel Abrahams, a doctoral student in Steel’s research group. Abrahams helped develop quantum diamond microscopes during his master’s in physics at the Quantum Nano Sensing Lab in Melbourne, Australia before moving onto the Oxford Interdisciplinary Bioscience Doctoral Training Programme.
The MFPs were inspired by the work of study co-authors Maria Ingaramo and Andy York, both then working for Calico Life Sciences. They had observed a small change in fluorescence when a magnet interacted with a quantum-enabled protein, explains Abrahams. “That was really cool! I hadn’t seen anything like that, and there were clearly potential applications if it could be made better,” he says.
Steel tells Physics World that “a lot of the past work in quantum biology was with fragile proteins, often at cryogenic temperatures. Surprisingly you could easily measure these MFPs in single living cells every few minutes as they can work for a long time at room temperature”. Furthermore, using MFPs only requires adding a magnet to existing fluorescence microscopy equipment, allowing new data to be cost-effectively obtained.
“For instance, you might use three or four fluorescent proteins to tag natural processes in a mammalian cell in a petri dish to see when they are being used and where they go. We could instead tag with 10 or 15 MFPs, allowing you to measure extra targets by just applying a magnetic field,” Steel explains.
Quantum engineer Peter Maurer from the University of Chicago in the US, who was not involved in the study, is enthusiastic about these new MFPs. “By combining magnetic fields and fluorescence, this work establishes an exciting new imaging modality with broad potential for future evolution. Notably, similar approaches could be directly applicable to qubits [quantum bits], such as the fluorescent protein qubits our team published in Nature last year,” he says.
Next, Steel intends to improve their instrumentation for using MFPs – much of which was adopted from researchers investigating how birds navigate via the earth’s magnetic field. Future MFP applications could include microbiome studies sensing where bacteria travel in our bodies, and the development of highly controllable actuators for drug delivery. “If you would like to turn on the protein’s ability to bind to a cancer cell, for example, you could simply put a magnet on the outside of a person in the right location,” he concludes.
The post New quantum-enabled proteins could improve biosensing appeared first on Physics World.
