ARTICLES https://doi.org/10.1038/s41557-018-0047-2 © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 1 Advanced Science Research Center, Graduate Center, City University of New York, New York, NY, USA. 2 Department of Chemical Engineering and Materials Science, University of California, Irvine, Irvine, CA, USA. 3 Department of Chemistry, Hunter College, City University of New York, New York, NY, USA. 4 Biochemistry and Chemistry Ph.D. Programs, The Graduate Center of the City University of New York, New York, NY, USA. 5 Department of Chemistry, University of California, Irvine, Irvine, CA, USA. *e-mail: rein.ulijn@asrc.cuny.edu M olecular encoded building blocks enable the assembly of supramolecular materials with precisely controlled shapes and functions, with tremendous potential applications in wide-ranging fields from biomedicine to energy materials 1–7 . Beyond supramolecular equilibrium structures, which are encoded at the molecular level by the chemical nature of the building blocks, it is increasingly recognized that the regulation of kinetic aspects of assembly opens up tremendous opportunities for the design of materials where the functional state does not represent chemical equilibrium 8–12 , giving rise to new features, such as materials with transient existence 13–15 , oscillations 16,17 , replication 18,19 , evolution- like adaption 20 and transient nanostructures activated by biocata- lytic cascades that influence cell fate 21 . While supramolecular design can give rise to predictable assemblies with varying structures and functions, the ability to actively change or edit the supramolecular assembly instructions (or code) in situ represents a new direction in supramolecular materials design. To effectively interface living and non-living matter for future therapeutic and diagnostic applications, it has been proposed that the dimensions, mechanical properties and general working principles of nature’s dynamic materials should be considered 22 . Living organ- isms are not composed of thermodynamic on/off switches. Instead, they operate by signalling and metabolic pathways composed of interconnected biocatalytic reactions that control and direct the for- mation and degradation of functional components. Incorporation of these concepts into supramolecular materials design is an active area of research, enabling richer materials responses 11,17,22,23 , which may ultimately be (near-) seamlessly integrated with biological sys- tems to measure, correct and direct biological function. One particularly versatile class of self-assembling materials are those based on peptides 3,9,24 . Even short peptides (two or three amino acids) contain sufficient chemical information to form organic nanomaterials with rich sequence-dependent proper- ties 25–29 . Furthermore, combining short peptides with non-biolog- ical functional molecules, such as organic semiconductors 27,30–34 , gives rise to materials properties that are not accessible to biological or synthetic systems alone. Kinetic aspects of peptide self-assembly can be controlled by in situ formation of self-assembling structures through (bio-) catalytic self-assembly 35,36 . This approach may be used for in situ formation of the peptide building blocks through amide bond formation reactions, either under kinetic 37,38 or ther- modynamic control 39 . Given the strong dependence of self-assembly behaviour on pep- tide sequence, increased interest in controlling kinetics of assembly, and the promise of in situ editing of molecular code to control self- assembly properties, we asked whether it would be possible to use catalytic incorporation of a variety of amino acids around one core functional assembly unit to access a multitude of possible assembly pathways (Fig. 1a,b). Moreover, by using activated functional pre- cursors 13 and taking advantage of enantioselectivity of biocatalysis, the assembly would enable built-in kinetic selection and competi- tion, giving rise to materials properties that can be actively regu- lated in terms of shape, composition, chirality and function over time. We based the system on a self-assembling organic semicon- ductor naphthalene diimide (NDI) (Fig. 1a), with the objective of producing materials that display transient electronic properties in water 40 , of future relevance to the dynamic interfacing of electronics with biological systems, for example in neuronal interfacing. Results Our active biocatalytic amino-acid-encoding approach is based on a bola-type amphiphile core with built-in chemical and kinetic Amino-acid-encoded biocatalytic self-assembly enables the formation of transient conducting nanostructures Mohit Kumar 1 , Nicole L. Ing 2 , Vishal Narang 1 , Nadeesha K. Wijerathne 1,3,4 , Allon I. Hochbaum 2,5 and Rein V. Ulijn 1,3,4 * Aqueous compatible supramolecular materials hold promise for applications in environmental remediation, energy harvest- ing and biomedicine. One remaining challenge is to actively select a target structure from a multitude of possible options, in response to chemical signals, while maintaining constant, physiological conditions. Here, we demonstrate the use of amino acids to actively decorate a self-assembling core molecule in situ, thereby controlling its amphiphilicity and consequent mode of assembly. The core molecule is the organic semiconductor naphthalene diimide, functionalized with D- and L- tyrosine methyl esters as competing reactive sites. In the presence of α-chymotrypsin and a selected encoding amino acid, kinetic competition between ester hydrolysis and amidation results in covalent or non-covalent amino acid incorporation, and variable supramo- lecular self-assembly pathways. Taking advantage of the semiconducting nature of the naphthalene diimide core, electronic wires could be formed and subsequently degraded, giving rise to temporally regulated electro-conductivity. 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