CryoEM reveals the complex self-assembly of a chemically driven disulfide hydrogel

Inspired by the adaptability of biological materials, a variety of synthetic, chemically driven self-assembly processes have been developed that result in the transient formation of supramolecular structures. These structures form through two simultaneous reactions, forward and backward, which generate and consume a molecule that undergoes self-assembly. The dynamics of these assembly processes have been shown to differ from conventional thermodynamically stable molecular assemblies. However, the evolution of nanoscale morphologies in chemically driven self-assembly and how they compare to conventional assemblies has not been resolved. Here, we use a chemically driven redox system to separately carry out the forward and backward reactions. We analyze the forward and backward reactions both sequentially and synchronously with time-resolved cryogenic transmission electron microscopy (cryoEM). Quantitative image analysis shows that the synchronous process is more complex and heterogeneous than the sequential process. Our key finding is that a thermodynamically unstable stacked nanorod phase, briefly observed in the backward reaction, is sustained for similar to 6 hours in the synchronous process. Kinetic Monte Carlo modeling show that the synchronous process is driven by multiple cycles of assembly and disassembly. The collective data suggest that chemically driven self-assembly can create sustained morphologies not seen in thermodynamically stable assemblies by kinetically stabilizing transient intermediates. This finding provides plausible design principles to develop and optimize supramolecular materials with novel properties. We elucidate the mechanisms of chemically driven self-assembly processes, demonstrating how synchronous assembly-disassembly reactions can stabilize transient structures and create morphologies that differ from conventional assemblies.

Automated summary

Inspired by biological materials, researchers have developed chemically driven self-assembly processes that can create transient supramolecular structures. The dynamics of these processes differ from conventional thermodynamically stable assemblies. Through time-resolved cryoEM analysis, the researchers found that the synchronous process of chemically driven self-assembly is more complex and heterogeneous than the sequential process. They also discovered that the synchronous process can sustain a thermodynamically unstable nanorod phase for several hours. This finding suggests that chemically driven self-assembly can create sustained morphologies not seen in thermodynamically stable assemblies by stabilizing transient intermediates kinetically.