Cornell Researchers Develop Innovative Protein Tracking Methodology

Cornell University researchers have unveiled a groundbreaking methodology for observing protein behavior within living cells, utilizing the cells' natural components as intrinsic sensors. This innovative approach, detailed in a study published on July 1, 2025, in *Nature Communications*, could significantly enhance the accuracy of molecular tracking and contribute to a deeper understanding of various biological processes, including those related to diseases such as cancer and neurodegeneration.

The research team, led by Dr. Brian Crane, the George W. and Grace L. Todd Professor in the Department of Chemistry and Chemical Biology and director of the Weill Institute for Cell and Molecular Biology, explored the use of flavins—vitamin B2-derived molecules that exhibit magnetic properties—as built-in sensors. This novel application allows for the tracking of protein interactions and organization within cells without the interference typically caused by synthetic tags.

"By employing natural proteins produced by the cell, we can gain insights into molecular behavior without disrupting cellular processes," stated Dr. Crane. The research utilized electron spin resonance (ESR) spectroscopy, a technique analogous to MRI but capable of detecting nanoscale changes. By leveraging the magnetic characteristics of flavoproteins, the team successfully tracked how proteins organize and move within living cells, representing a significant advancement in cell biology research.

Lead author Timothée Chauviré, a research associate in Crane's lab, noted that the magnetic spin states of the flavoproteins were unexpectedly stable in a cellular environment. The researchers demonstrated this method's capabilities by studying Aer, a bacterial protein that aids E. coli in oxygen sensing. This marked the first instance of direct observation of the Aer receptor's assembly within a living cell, revealing how these proteins can form higher-order structures that amplify signaling processes.

The implications of this research extend beyond mere observation. The methodology presents a promising tool for studying complex biological mechanisms that underpin various diseases. According to Dr. Jack H. Freed, professor emeritus in the Department of Chemistry and Chemical Biology and a contributor to the study, the ability to visualize these processes in real-time could illuminate the pathways of viral assembly or protein misfolding, critical factors in cancer and neurodegeneration.

Funding for this study was provided by reputable institutions, including the National Science Foundation and the National Institutes of Health, underscoring the research's significance in the scientific community.

As the team prepares to adapt this methodology for use in mammalian cells, the potential for broader applications in understanding cellular processes and disease mechanisms becomes increasingly apparent. The research represents a pivotal step forward in the field of molecular biology, offering new avenues for exploration in understanding and treating complex diseases.

In summary, the Cornell researchers' innovative use of natural cellular components as sensors provides a promising new direction for studying molecular interactions in live cells, paving the way for advancements in both basic and applied biomedical research.