No abstract

The production of functional molecular architectures through self-assembly is commonplace in biology, but despite advances, it is still a major challenge to achieve similar complexity in the laboratory. Self-assembled structures that are reproducible and virtually defect free are of interest for applications in three-dimensional cell culture, templating, biosensing and supramolecular electronics. Here, we report the use of reversible enzyme-catalysed reactions to drive self-assembly. In this approach, the self-assembly of aromatic short peptide derivatives provides a driving force that enables a protease enzyme to produce building blocks in a reversible and spatially confined manner. We demonstrate that this system combines three features: (i) self-correction--fully reversible self-assembly under thermodynamic control; (ii) component-selection--the ability to amplify the most stable molecular self-assembly structures in dynamic combinatorial libraries; and (iii) spatiotemporal confinement of nucleation and structure growth. Enzyme-assisted self-assembly therefore provides control in bottom-up fabrication of nanomaterials that could ultimately lead to functional nanostructures with enhanced complexities and fewer defects.

Supramolecular gels, which demonstrate tunable functionalities, have attracted much interest in a range of areas, including healthcare, environmental protection and energy-related technologies. Preparing these materials in a reliable manner is challenging, with an increased level of kinetic defects observed at higher self-assembly rates. Here, by combining biocatalysis and molecular self-assembly, we have shown the ability to more quickly access higher-ordered structures. By simply increasing enzyme concentration, supramolecular order expressed at molecular, nano-and micro-levels is dramatically enhanced, and, importantly, the gelator concentrations remain identical. Amphiphile molecules were prepared by attaching an aromatic moiety to a dipeptide backbone capped with a methyl ester. Their self-assembly was induced by an enzyme that hydrolysed the ester. Different enzyme concentrations altered the catalytic activity and size of the enzyme clusters, affecting their mobility. This allowed structurally diverse materials that represent local minima in the free energy landscape to be accessed based on a single gelator structure.M olecular self-assembly 1-7 can be controlled using a variety of stimuli, including chemical 8,9 and mechanical 10 triggers, as well as X-rays 11 . Although the traditional premise in selfassembly suggests that supramolecular material properties can be fully encoded into molecular building blocks, it is increasingly apparent that the chosen self-assembly pathway is central to the final structure and its material functionality. Biocatalytic control of self-assembly systems is a novel direction for laboratory-based self-assembly 12-17 , although it is omnipresent in the biological world. Indeed, enzymatically controlled self-assembly and disassembly underlies vital processes such as cell movement, intracellular transport and muscle contraction. In chemists' hands, the combination of biocatalysis and molecular self-assembly has recently emerged as a powerful new approach to make novel stimuli-responsive molecular materials [12][13][14][15][16][17] . We believe that catalytic control of self-assembly provides important new methodology beyond such triggering of material transitions. In particular, the combination of biological selectivity, localized action and operation under constant, physiological conditions provides a new methodology for bottomup nanofabrication of future soft materials and devices, allowing for unprecedented control of supramolecular order.Here, we focus on the control of supramolecular order with few defects. In principle, there are two possible approaches to defect reduction-either improving the fidelity of the self-assembly process (avoiding defects) or using fully reversible systems that operate under thermodynamic control (repairing defects). The latter approach is generally slow and only applicable to cases where the desired structure represents the global equilibrium state and where the system is fully reversible, that is, under thermodynamic control 16 . Many structure...