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

Paul Joshua Hurst; Justin T Mulvey; Rebecca A Bone; Serxho Selmani; Redford F Hudson; Zhibin Guan; Jason R Green; Joseph P Patterson

doi:10.1039/d3sc05790a

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

Chem Sci. 2023 Dec 18;15(3):1106-1116. doi: 10.1039/d3sc05790a. eCollection 2024 Jan 17.

Authors

Paul Joshua Hurst^{1

2}, Justin T Mulvey^{2

3}, Rebecca A Bone⁴, Serxho Selmani^{1

2}, Redford F Hudson⁵, Zhibin Guan^{1

2

3

6

7}, Jason R Green^{4

8}, Joseph P Patterson^{1

2

3}

Affiliations

¹ Department of Chemistry, University of California, Irvine Irvine California 92697 USA patters3@uci.edu.
² Center for Complex and Active Materials, University of California, Irvine Irvine California 92697 USA.
³ Department of Materials Science and Engineering, University of California, Irvine Irvine California 92697 USA.
⁴ Department of Chemistry, University of Massachusetts Boston Boston Massachusetts 02125 USA.
⁵ Department of Computer Science, University of California, Irvine Irvine California 92697 USA.
⁶ Department of Chemical and Biomolecular Engineering, University of California, Irvine Irvine California 92697 USA.
⁷ Department of Biomedical Engineering, University of California, Irvine Irvine California 92697 USA.
⁸ Department of Physics, University of Massachusetts Boston Boston Massachusetts 02125 USA.

Abstract

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 ∼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.