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Quantum physics is going through a “second revolution”, all focused on applications. Quantum technologies promise to change everything. Is it finally biology’s turn?
Today, we turn fluorescent proteins into quantum sensors. Will they survive the test? Read to find out!
And yes, we’ve seen something similar not too long ago. It’s a popular topic!
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But now, let’s go!
Proteins Go Quantum
Scientists engineered fluorescent proteins to turn them into quantum sensors and used them to localize cells with magnetic fields. Image credits: Nature.
Fluorescent Proteins: Biology’s Jack of All Trades
Fluorescent proteins are the scientist’s best friend.
For decades, researchers have relied on green fluorescent protein (GFP) and its cousins to track what’s happening inside cells. You need a different color? A faster-folding protein? Something more stable? You just have to choose!
And applications are endless.
They can label proteins to localize them inside cells. They can measure mechanical forces, report on pH, or check whether drugs are going in the right place. Fluorescent proteins are the first tool you reach for to watch biology in action!
But what if they could do even more? What about a quantum twist?
Quantum Biosensing
Quantum sensors use “quantum systems” (spins, atoms, ions, or photons) as probes.
These systems are extremely sensitive to changes in their environment (temperature, pH, magnetic or electric fields). If you can read out these changes, you can build crazy precise sensors!
For us bio-focused, this could mean:
Mapping magnetic fields in neurons
Tracking chemical reaction in real time
Measuring changes inside single molecules or electrons!
Who knows what kinds of new biology this could reveal?
Well, some scientists are already bringing quantum sensing into biology. Nitrogen-vacancy diamonds and quantum dots can map nanoscale magnetic fields and have even been used inside cells!
The big challenges? Delivery, targeting, and toxicity.
Plus, these versatile sensors are not optimized for the “messy” conditions you find inside cells! They work much better in the controlled conditions of semiconductor manufacturing, for example.
But you know what is optimized for life inside cells? Oh yeah, fluorescent proteins!
Bridging Quantum and Bio
Now, are fluorescent proteins quantum sensors already? No.
But they bring some great advantages over other quantum systems:
They’re biocompatible.
Cells can produce them directly at specific locations, eliminating delivery or targeting problems.
They are (relatively) easy to engineer by changing DNA sequences.
All we need is a fluorescent protein that can act like a quantum sensor!
Worry not, today’s paper has you covered.
The authors engineered flavin-binding proteins called MagLOV, whose fluorescence responds to magnetic fields! Using directed evolution, they created improved variants (MagLOV2 and MagLOV2 fast) that are even more optimized for quantum sensing.
MagLOVs show two effects crucial for quantum sensors:
Large fluorescence magnetic-field effects (MFEs): Expose MagLOV2 to a magnetic field, and its fluorescence can drop by as much as 50%!
Optically detected magnetic resonance (ODMR): If you combine a magnetic field with microwaves at just the right frequency, you can influence the quantum state of the protein. How do you detect it? Simple: this quantum shift reduces fluorescence!
The craziest part? All this works at room temperature, inside living bacterial cells!
In other words, the authors created a genetically encoded quantum sensor that works inside living cells. Incredible!
Deep in the Mechanism
Now, I’m no physicist, you know that.
I’ll do my best to explain how this whole thing works, but I can’t guarantee anything. Feel free to skip ahead to the applications! Or get someone more qualified to explain quantum physics to you…
Ready? Let’s try!
The core idea behind MFEs is this.
When light hits the protein, it excites a molecule called FMN (flavin mononucleotide). This excitation triggers an electron transfer from a nearby amino acid, creating a radical pair (a transient molecular species containing unpaired electrons).
This pair has a quantum property called spin.
The spin state is not an actual spin, like a ball. It’s a property of a particle, like charge or mass. You can think of it as a quantum “compass needle” that “points” up or down (or up and down, because of quantum physics…).
Going back to our proteins, the radical pair has two possible spin states:
Singlet state (S)
Triplet state (T)
These states lead to different outcomes
Singlet → radicals recombine → fluorescence
Triplet → radicals separate → no fluorescence
At any given time, the radical pair oscillates between singlet and triplet.
Just like real-life compasses, magnetic fields interact with spin. They shift the balance between singlet and triplet, changing how often the radicals recombine. And the brightness of the protein becomes magnetic-field dependent!
That’s MFE for you!
Fun fact: this is similar to how birds detect magnetic fields! Fluorescence included.
Now, what about ODMR?
For ODMR (optically detected magnetic resonance), we add an ingredient: microwaves. When the microwave frequency matches the resonance frequency of the electron spins, it flips them between spin states. That changes the singlet–triplet balance again.
This controls fluorescence, and you can detect the resonance frequency optically.
Congrats, you just created a protein-based quantum sensor!
Applications: Imaging with Quantum Sensors
Okay, I hope you’re still with me after all that.
If that wasn’t impressive enough, the authors didn’t stop at proving the mechanism or evolving better MagLOVs. No, they showed a path for these sensors to be useful!
They focused on 3 applications:
Multiplexing and lock-in signal recovery
MagLOV variants respond to magnetic fields with slightly different timing. The authors used this to label cell populations with different MagLOV variants and distinguish mixed populations. And by focusing (locking-in) on the MFE, they detected cells with extremely weak MagLOV expression mixed with eGFP cells of the same color. A smart strategy to extract signals in high-noise environments like cells!
Microenvironment sensing
The authors diluted MagLOV2-fast in gabudotrol, a paramagnetic contrast agent used in clinical MRI. This compound affects the local spin microenvironment; can the proteins detect it? Yes! The MFE contrast was reduced in the presence of gabudotrol, with a nice dose-response to boot.Spatial localization with fluorescence MRI
I saved the coolest experiment for last! The team modified a small MRI machine and turned it into a hybrid fluorescence microscope-MRI. Using it and MagLOV as a sensor, they localized two bacterial cell bands embedded inside a silicon block. The proteins would light up only when hit with the right frequency at the right location. A great proof of concept for scattering-insensitive fluorescence localization!
Quantum Comes for Biology
A super cool paper!
It’s crazy to see the progress here. I’ve read somewhere that the field is experiencing a “second revolution”. It really feels that way! The first discovered the fundamental principles. This second time, it’s all about applications!
And the intersection with biology is exciting! There are lots of quantum-based processes in biology, from cellular respiration to enzyme catalysis and photosynthesis. These new tools will allow us to study and manipulate these systems even better!
This paper is a great example. It shows how directed evolution can be used to improve existing magneto-responsive proteins. Scientists have been doing this for decades: we’re good at it!
So, it’s cool to see fluorescent proteins turned into genetically encoded quantum probes! Leveraging all the strengths of biological systems. This system still has limitations in signal strength, photophysics, and translation to complex systems, of course.
But it’s an incredible first step into biological quantum sensing!
So, go here and read all the details of this awesome work!
If you made it this far, thank you! What do you think of quantum sensing? Do you think it has a place in biomedicine? Reply and let me know!
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More Room:
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Lighting Up mRNA: Imaging RNA inside the cells is important for biological studies, but current tools have limitations. In this study, the authors engineer conditionally stable MS2 and PP7 coat proteins that degrade unless bound to their target RNA, reducing background fluorescence in live-cell imaging. These probes enable sensitive single-mRNA visualization and allow dual-color imaging of different RNA species in the same cell. The approach improves the accuracy and versatility of RNA tracking in living cells.