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Enzyme-assisted self-assembly under thermodynamic control

Abstract

The production of functional molecular architectures through self-assembly is commonplace in biology, but despite advances1,2,3, 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 culture4,5, templating6, biosensing7 and supramolecular electronics8. Here, we report the use of reversible enzyme-catalysed reactions to drive self-assembly. In this approach, the self-assembly of aromatic short peptide derivatives9,10 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 libraries11,12,13; 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.

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Figure 1: Enzyme-assisted self-assembly under thermodynamic control.
Figure 2: Enzyme-assisted self-assembly of Fmoc-peptide derivatives.
Figure 3: Enzyme-driven dynamic combinatorial library.
Figure 4: Spatial confinement of nucleation and growth.

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Acknowledgements

We thank the Engineering and Physical Sciences Research Council and the Leverhulme Trust for funding, P. Crook for assistance with infrared spectroscopy, S. Todd for assistance with surface modification, P. Coppo and T. Jowitt for assistance with fluorescence, and V. Barittini for mass spectrometry. N.H. acknowledges the support of the UK Centre for Tissue Regeneration (a partnership between NorthWest Development Agency and University of Manchester, UK). R.V.U. acknowledges P. Halling for his careful reading of the manuscript and for providing helpful suggestions.

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R.V.U. conceived the concepts and helped design the experiments. R.J.W., A.K.D., A.M.S., R.C. and N.H. designed and performed the experiments and analysed the data. All authors co-wrote the paper.

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Correspondence to Rein V. Ulijn.

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Williams, R., Smith, A., Collins, R. et al. Enzyme-assisted self-assembly under thermodynamic control. Nature Nanotech 4, 19–24 (2009). https://doi.org/10.1038/nnano.2008.378

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