ASU professor opens new window into protein motion

Proteins are always on the move. These tiny biological machines bend, twist, and shift to carry out nearly every function in the body, from fighting off infections to keeping your cells alive.

But for decades, scientists had a blind spot: they couldn’t easily detect how proteins move on the nanosecond-to-microsecond timescale. These motions, obscured by molecular tumbling, are too slow for many conventional techniques but also too fast for others.

Now, new research from Mouzhe Xie, assistant professor in Arizona State University’s School of Molecular Sciences and his collaborators helps close the gap.

In a study recently published in Nature Protocols, Xie and his collaborators from The Ohio State University detail a new technique they’ve developed called Nanoparticle-Assisted NMR Spin Relaxation (NASR) that lets scientists see protein motions that are otherwise inaccessible.

“We developed a method that takes advantage of nanoparticles to extend a conventional experiment that used to be limited up to nanoseconds,” Xie said. “Now we extend the detection window further to the slower microsecond region, and with that we cover all of the timescales that can be studied by a conventional NMR spectroscopy. It pushes the field forward.”

The concept behind NASR is surprisingly simple; by adding silica nanoparticles, microscopic glass beads, to protein samples in solution, the team was able to slow down the protein’s tumbling just enough to make their slower internal motions detectable using standard NMR spectroscopy.

The technique opens new doors for studying the inner dynamics of proteins involved in critical biological functions and diseases.

Xie has always let his curiosity guide his research, developing new technologies to explore phenomena previously out of reach.

During his undergrad years at Xiamen University in China, Xie was introduced to the world of nanoparticles, super small materials with unique properties. As a student, his research revolved around designing and modifying nanoparticles for potential use in medicine or biology.

Later, while pursuing his PhD at The Ohio State University, he shifted gears to study the dynamics and functions of proteins using nuclear magnetic resonance (NMR) spectroscopy, a technique that uses magnetic fields and radio waves to study the structure and motion of molecules.

He soon realized that his former research interests could help better inform his new ones.

“Conventional NMR experiments could only detect either very fast or very slow motions, not things happening on the nanosecond-to-microsecond timescales,” Xie said. “But a lot of important protein internal dynamic processes happen right in this regime, and we weren’t seeing them.”

Xie and his team introduced silica nanoparticles into the solution where the proteins were floating. These beads don’t directly stick to the proteins or change their shape. Instead, they rapidly absorb and release protein molecules in a random manner just enough to slow down the overall tumbling motion.

That small slow-down made a big difference.

The work extended a broader observation window that stretched from nanoseconds to microseconds, all without needing any new equipment.

For Xie, NASR is more than just a technical achievement. It’s a personal milestone. The method is the culmination of nearly a decade of investigation, not just by Xie but by multiple generations of PhD students who expanded on the original idea.

“I was the first one who came up with the concept during my PhD journey a while back,” Xie said. “But it took years of work, and the contributions of at least three other PhD students, to build the complete picture.”

Publishing the method as a protocol, a step-by-step guide for other labs to follow, also marks a turning point for Xie.

“You don’t publish a protocol unless you’re confident,” Xie said. “It means the method is ready to be used by others.”

That’s exactly what excites him.

With NASR now in the hands of the scientific community, Xie hopes it opens new doors in fields ranging from biochemistry to drug discovery.

“It’s not about our work anymore,” he said. “It’s about what this method can help others discover.”

Xie's research now ventures into the emerging field of quantum sensing technologies.

At ASU, he leads a team developing quantum sensing technology for biology and medicine and is a steering committee member of ASU's Quantum Collaborative established to embrace the growing global wave of quantum research.

The United Nations declared 2025 the International Year of Quantum Science and Technology.

“This is not a departure from the NASR work, but rather builds on its momentum,” Xie said. “Many underlying principles, such as magnetic resonance, remain the same and are central to quantum information science.”

Xie’s lab is developing quantum sensors based on a crystal defect in diamond to perform NMR experiments.

Compared to the traditional NMR apparatus, this novel diamond quantum sensor allows the detection of NMR signals from exquisitely small sample volume, even down to a single cell or a single molecule. It opens up a new avenue to make biological discoveries and medical breakthroughs.

“We hope to contribute to the development of quantum sensing technologies that arise at the intersections of different research fields and mature into widely applicable tools,” Xie said. “Much like the success of NASR.”