Studying what goes on inside a living cell almost always requires disturbing it. Most methods rely on introducing a probe — a fluorescent tag, a foreign sensor protein, sometimes a piece of engineered DNA — and any of those can alter the very biology the experiment is trying to measure. A 2025 paper in Nature Communications from a team at Cornell describes an alternative: using proteins that cells already produce as their own reporters.
The proteins in question are flavoproteins, a broad family that contains a flavin cofactor at their core. Flavins are involved in dozens of metabolic and electron-transfer reactions across most kingdoms of life, and they have a useful physical property — they exhibit magnetic and optical signals that depend sensitively on their immediate chemical environment.
The Cornell team showed that by reading those signals, researchers can pull out information about local conditions inside the cell — pH, redox state, the presence of certain binding partners — without introducing anything new. The flavoproteins are not engineered. They are already there, doing their normal jobs. The measurement is non-invasive in a strict sense.
What this enables, in practice, is a closer look at cellular biology in its native state. The authors used the technique to track flavoprotein behavior in real time and showed that the signals shifted in response to specific metabolic perturbations. Because the approach relies on endogenous biology rather than engineered probes, it should be portable across cell types and organisms without needing to redesign tools for each new system.
The method does not replace traditional probes — they remain more flexible for certain applications, particularly when researchers want to target a specific structure or pathway that flavoproteins do not naturally interact with. But for studies where the central goal is to observe cells as undisturbed as possible, the technique offers a useful new option.