Imagine a tiny locomotive gliding back and forth along an invisible track, powered solely by its own energy. At the molecular scale, this captivating image embodies the revolutionary concept of molecular motors—complex systems that could revolutionize materials science, enhance targeted drug delivery, and facilitate the creation of nanoscale robots.

Since the inception of synthetic molecular machines in 1994, driven by nature's own biological counterparts, researchers have made significant strides in this field. This endeavor was honored with the 2016 Nobel Prize in Chemistry, recognizing pivotal achievements in molecular machine design.

Among the most promising candidates in molecular motor research is polypseudorotaxane, a structure crafted from a poly(ethylene glycol) (PEG) polymer chain threaded through multiple α-cyclodextrin (α-CD) rings. These rings engage in self-assembly in aqueous solutions, intelligently moving along the length of the PEG chain. Yet, the intricate details behind their movement remained shrouded in mystery—until now.

Recently, a team from the Japan Advanced Institute of Science and Technology (JAIST), led by Associate Professor Ken-ichi Shinohara, achieved a significant breakthrough. They successfully visualized the dynamic motion of α-CD rings along the PEG chain in real time. Utilizing fast-scanning atomic force microscopy (FS-AFM), the researchers captured stunning images of the shuttling rings, unveiling previously elusive localized structural changes.

Published in Macromolecules on March 4, 2025, this study introduces a pioneering method for analyzing the structural intricacies of supramolecular polymers—an unprecedented advance that may accelerate the development of sophisticated molecular machines.

Dr. Shinohara stated, “Although the PEG@α-CD polypseudorotaxane is widely utilized, the structural transformations that occur during the shuttling of α-CD rings along the polymer chain have not been thoroughly understood. By revealing its structure at the solid–liquid interface, our research will significantly contribute to the advancement of synthetic polymer motors harnessed by thermal fluctuations.”

For their research, the team meticulously mixed PEG100k with α-CD in an aqueous solution, allowing it to settle for over six hours to form a white solid. They then conducted their analysis in a potassium chloride aqueous solution using FS-AFM. Unlike traditional optical microscopes, AFM uses a finely tuned tip on a nanoscale lever to meticulously scan surfaces, producing high-resolution images of the smallest structural features.

Initial imaging of the PEG100k chain revealed its flexible, dumbbell-shaped architecture, complete with globular structures at each end. This inherent flexibility endowed the chain with spring-like properties, leading to vast expansions and contractions; in a relaxed state, its length averaged just 48.1 nm, compared to a full extension of 790 nm.

Adding α-CD rings altered the dynamics significantly, decreasing the chain’s flexibility while increasing its average length to 499.6 nm. The resulting PEG100k@α-CD polypseudorotaxane appeared notably more rigid, with end-cap formations effectively keeping the α-CD rings securely in place. Fascinatingly, though less flexible, the chain maintained spring-like motions, as the α-CD rings continued to shuttle along its structure.

Dr. Shinohara observed, “We noted that the polypseudorotaxane exhibited motions of contraction and extension driven by the shuttling of α-CD rings. These movements were primarily observed in the exposed, self-shrinking segments of PEG, indicating that the α-CD rings’ movements caused repeated expansions and contractions.”

To further validate their findings, the researchers conducted molecular dynamics simulations, which replicated the observed shrinking and extending motions captured in the FS-AFM experiments. Although achieving fully functional molecular machines is an ambitious long-term objective, this investigation lays critical groundwork for comprehensively understanding molecular movements within supramolecular systems.

As Dr. Shinohara pointed out, “FS-AFM represents a promising methodology for analyzing supramolecular materials, particularly when traditional spectroscopic methods fall short.”

The insights gained from this research hold immense potential for developing energy-efficient molecular motors capable of harnessing thermal energy at room temperature, a breakthrough that could pave the way for innovations in numerous fields, from sustainable energy solutions to novel medical applications. Stay tuned as this groundbreaking research continues to unfold, possibly reshaping our understanding of molecular machinery and its myriad applications!