Scientists visualize α-cyclodextrin rings moving along a polymer using fast-scanning atomic force microscopy, aiding molecular machine design
Ishikawa, Japan -- Imagine a microscopic locomotive moving back and forth along a track, propelling itself without any external force. At the molecular level, this concept forms the foundation of molecular motors—intricate systems that could enable advanced materials, targeted drug delivery, and the development of nanoscale robotics.
Inspired by nature’s molecular machines, scientists have been developing artificial counterparts since the first synthetic molecular machine was created in 1994. This research has progressed rapidly, culminating in the 2016 Nobel Prize in Chemistry for breakthroughs in molecular machine design. One promising candidate is polypseudorotaxane, a structure where a poly(ethylene glycol) (PEG) polymer chain is threaded through multiple α-cyclodextrin (α-CD) rings. In aqueous solutions, these rings self-assemble onto the PEG chain and move along its length. However, the specific structural changes behind this movement have remained unclear—until now.
Recently, scientists from the Japan Advanced Institute of Science and Technology (JAIST) have visualized the dynamic shuttling of α-CD rings along the PEG chain in real time, revealing localized structural changes that were previously unclear. Using a specialized microscope called fast-scanning atomic force microscopy (FS-AFM), the team, led by Associate Professor Ken-ichi Shinohara, captured real-time images of α-CD rings moving along the PEG chain. Their study, published in
Macromolecules on March 4, 2025, introduces a new method for analyzing the structure of supramolecular polymers—an approach that was previously unattainable and could pave the way for more advanced molecular machines.
“Although PEG@α-CD polypseudorotaxane is widely used, the structural changes that occur as α-CD rings shuttle along the polymer chain remain poorly understood. By revealing its structure at the solid–liquid interface, our study will contribute to the development of synthetic polymer motors driven by thermal fluctuations,” explains Dr. Shinohara.
To prepare the polypseudorotaxane, the researchers mixed PEG
100k with α-CD in an aqueous solution and allowed the sample to rest for more than six hours. This process led to the formation of a white solid, which they then analyzed using FS-AFM in a 15 millimolar potassium chloride aqueous solution. Unlike regular optical microscopes, AFM uses an ultra-sharp tip on a tiny lever to scan surfaces, capturing nanoscale features and generating high-resolution images.
Imaging of the PEG
100k chain alone revealed a highly flexible, dumbbell-shaped structure with globules at both ends. This flexibility gave it spring-like properties, allowing it to expand and contract freely. As a result, when relaxed, the chain appeared much shorter (averaging 48.1 nm) than its actual stretched-out length of 790 nm. When α-CD rings were added, they reduced the chain’s flexibility. Imaging the PEG
100k@α-CD polypseudorotaxane showed a significantly longer (499.6 nm on average) and a more rigid structure, with the end-cap formations preventing the α-CD rings from slipping off. Interestingly, despite being less flexible, the chain still exhibited a spring-like motion, as α-CD rings continued to shuttle along its length.
“We observed that the polypseudorotaxane exhibited shrinking and extending motions driven by the shuttling of α-CD rings along the polymer chain. These movements mainly occurred in the exposed, self-shrinking PEG segments, where repeated expansion and contraction were observed as the α-CD rings moved,” explains Dr. Shinohara. Molecular dynamics simulations further confirmed these findings, reproducing the shrinking and extending motions observed in the FS-AFM experiments.
Although fully functional molecular machines remain a long-term goal, this study lays the groundwork for understanding molecular motion in supramolecular systems.
“FS-AFM is a promising technique for analyzing supramolecular materials, especially when conventional spectroscopic methods are unsuitable for structural analysis,” remarks Dr. Shinohara. These insights could lead to energy-efficient molecular motors that harness thermal energy at room temperature for controlled movement.
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Reference
| Title of original paper: |
Direct Observation of the “End-Capping Effect” of a PEG@α-CD Polypseudorotaxane in Aqueous Media |
| Authors: |
Ryoga Hori and Ken-ichi Shinohara |
| Journal: |
Macromolecules |
| DOI: |
10.1021/acs.macromol.4c02491 |
About Japan Advanced Institute of Science and Technology, Japan
Founded in 1990 in Ishikawa prefecture, the Japan Advanced Institute of Science and Technology (JAIST) was the first independent national graduate school in Japan. Now, after 30 years of steady progress, JAIST has become one of Japan’s top-ranking universities. JAIST strives to foster capable leaders with a state-of-the-art education system where diversity is key; about 40% of its alumni are international students. The university has a unique style of graduate education based on a carefully designed coursework-oriented curriculum to ensure that its students have a solid foundation on which to carry out cutting-edge research. JAIST also works closely with both local and overseas communities by promoting industry–academia collaborative research.
About Associate Professor Ken-ichi Shinohara from Japan Advanced Institute of Science and Technology, Japan
Ken-ichi Shinohara is an Associate Professor at the Materials Chemistry Frontiers Research Area, Japan Advanced Institute of Science and Technology (JAIST), specializing in nanomaterials chemistry, polymer chemistry, and nanobioscience. He earned his Ph.D. from Niigata University in 1997 and has held academic positions at JAIST and Tohoku University. His research focuses on biomimetic systems, molecular motors, supramolecular polymers, and advanced imaging techniques, including atomic force microscopy and scanning tunneling microscopy. With expertise in molecular machines and single-molecule measurements, he contributes to the development of functional nanomaterials and polymer-based molecular motors.
Funding information
This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI through a Grant-in-Aid for Scientific Research (B) (Grant No. 20H02546) and a Grant-in-Aid for Scientific Research (C) (23K04520) (K.S.) and JST SPRING (JPMJSP2102) (R.H.).