Imagine materials that build themselves, responding intelligently to their environment to deliver drugs precisely where needed, scaffold regenerating tissues, or clean up pollutants. These are the promises of supramolecular gels, fascinating soft materials formed by the spontaneous self-assembly of small molecules. But how exactly do these intricate structures emerge from a seemingly random soup of molecules? For years, this fundamental process remained hidden, occurring too quickly and at too small a scale to observe (Fig.1).
Now, for the first time, a collaborative research team in Japan has captured the entire nanoscale drama of supramolecular gel formation in real-time. Using the extraordinary capabilities of high-speed atomic force microscopy (HS-AFM), capable of recording molecular events as they happen, the researchers created a stunning "molecular movie" revealing the secrets of gelation. The footage delivered a surprise, overturning previous assumptions. Scientists expected to see tiny, thin fibrils forming first, gradually thickening into the final gel fibers (Fig 2a). Instead, the HS-AFM movie showed relatively thick supramolecular fibers appearing directly from the solution, seemingly skipping the intermediate step entirely (Fig 2b).
Even more intriguingly, these fibers grew in peculiar bursts – racing forward, pausing unexpectedly, then resuming their rapid growth (Fig. 3a). This unique "stop-and-go" behavior hinted at a completely new assembly mechanism. To decipher this molecular dance, the researchers proposed a novel "block-stacking model" (Fig. 3b). This theory suggests that molecular building blocks can only efficiently stack onto the fiber tip when its surface is uneven or "rough." When the tip momentarily becomes smooth during growth, stacking pauses until new irregularities form, allowing growth to restart. This elegant model was further validated as computer simulations based on it perfectly reproduced the observed stop-and-go dynamics.
Digging deeper with quantitative image analysis, the team mapped out the two distinct stages of gelation: an initial "nucleation" phase where molecules cluster into stable seeds, followed by the "growth" phase where fibers elongate from these seeds (Fig 2b). Their analysis was so precise they could even estimate the critical, tiny number of molecules required to form a stable nucleus – a rare and valuable insight into the very first moments of self-assembly. The ability to directly witness this molecular assembly process, rather than inferring it from indirect measurements, provides unambiguous evidence for how supramolecular gelation truly occurs.
By providing a clear view of the assembly pathway, this research offers a powerful new toolkit for designing next-generation supramolecular gels. Scientists can now potentially control gel properties – like stiffness, responsiveness, or drug release rate – by targeting specific stages of the formation process revealed in this study. This paves the way for accelerating the development of smarter, more effective materials for critical applications in medicine, biotechnology, and environmental remediation. The study, titled "Molecular-level insights into the supramolecular gelation mechanism of urea derivative", was published in the journal Nature Communications on 22 April 2025.
