Magnetic Protein Imaging: New Tech for Tracking Biological Processes in Living Cells

A newly discovered class of biomolecules, called magnetically sensitive fluorescent proteins (MFPs), holds promise for significantly improving how scientists visualize biological processes within living cells and could potentially pave the way for innovative therapies.

A New Window into Cellular Processes

Current fluorescent proteins, widely used in biological studies, respond only to light shone directly on them. This method can be imprecise because light scatters within tissues, making it difficult to pinpoint the exact origin of the fluorescence. MFPs, developed by a team led by Harrison Steel, head of the Applied Biotechnology Research Group at the University of Oxford in the UK, respond partially to both magnetic fields and predictably traveling radio waves that penetrate biological tissues without distortion.

How MFPs Work

Researchers detect the location of MFPs within living cells by applying a static magnetic field with a precisely known gradient and radiofrequency (RF) signals. These signals regulate the fluorescence triggered by light-emitting diodes (LEDs). The brightest fluorescence occurs when the RF signal aligns with the energy transitions of entangled electron systems present within the MFP. Because the resonance frequency depends on the strength of the surrounding magnetic field, the brightness reveals the protein’s location.

Did You Know? Researchers developed these MFPs through “directed evolution,” creating and testing thousands of DNA variations to identify those with the best fluorescent response to magnetic fields.

The development of MFPs, detailed in a recent publication in Nature, involved a process of “directed evolution.” Starting with a DNA sequence, the team created two to three thousand variations, selecting those with the strongest fluorescent response to magnetic fields and repeating the process multiple times. The resulting proteins were tested using ODMR (optically detected magnetic resonance) and MFE (magnetic field effect) experiments, confirming their ability to be detected in single living cells and sense their local environment.

Inspired by Quantum Interactions

The research was inspired by the work of Maria Ingaramo and Andy York, co-authors of the study who were previously with Calico Life Sciences. They observed small changes in fluorescence when a magnet interacted with quantum-activated proteins, as explained by Abrahams. “It was very cool! I hadn’t seen anything like that before, and it was clear there were potential applications if it could be improved,” she said.

According to Harrison Steel, speaking to Physics World, “much of past work in quantum biology has been done with fragile proteins, often at cryogenic temperatures. It’s surprising you can easily measure these MFPs in single living cells every few minutes because they can work for long periods at room temperature.” using MFPs requires only adding a magnet to existing fluorescence microscopy equipment, allowing for new data to be obtained cost-effectively.

Expert Insight: The ability to detect proteins within living cells without relying solely on light-based methods represents a significant advancement, potentially overcoming limitations inherent in traditional fluorescence microscopy.

“For example, you might use three or four fluorescent proteins to mark natural processes in mammalian cells in a petri dish to see when and where they are used. Instead, You can mark with 10 or 15 MFPs, allowing you to measure additional targets by simply applying a magnetic field,” Steel explained.

Future Applications and Potential

Peter Maurer, a quantum engineer from the University of Chicago in the US, who was not involved in the study, expressed enthusiasm for the new MFPs. “By combining magnetic fields and fluorescence, this research establishes an exciting new imaging modality with broad potential for future evolution. Notably, a similar approach could directly apply to qubits [quantum bits], such as fluorescent qubit proteins that our team published in Nature last year,” he said.

Steel intends to further refine their instruments to utilize MFPs, drawing on techniques developed by researchers studying how birds navigate using the Earth’s magnetic field. Potential future applications include studying the microbiome and tracking bacterial movement within the body, as well as developing highly controlled actuators for drug delivery. “If you wanted to activate a protein’s ability to bind to cancer cells, for example, you would simply place a magnet outside someone at the appropriate location,” Steel stated.

Frequently Asked Questions

How are MFPs different from traditional fluorescent proteins?

Traditional fluorescent proteins respond only to light, which can scatter and reduce accuracy. MFPs respond to both magnetic fields and radio waves, offering a more precise way to locate proteins within cells.

How were MFPs developed?

MFPs were developed through a process called “directed evolution,” where researchers created and tested thousands of variations of a DNA sequence to find those with the best response to magnetic fields.

What are some potential applications of MFP technology?

Potential applications include studying the microbiome, tracking bacterial movement, and developing targeted drug delivery systems.

Considering the potential for more precise biological imaging, how might this technology reshape our understanding of cellular processes and disease?