Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Biocatalytic induction of supramolecular order


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Biocatalytic self-assembly and gelation.
Figure 2: Spectroscopic and structural evidence of catalytically induced supramolecular order.
Figure 3: Evidence of catalytic clusters and cooperativity.


  1. Estroff, L. A. & Hamilton, A. D. Water gelation by small organic molecules. Chem. Rev. 104, 1201–1217 (2004).

    Article  CAS  Google Scholar 

  2. Lehn, J. M. Supramolecular Chemistry—Concepts and Perspectives (VCH Weinheim, 1995).

  3. Whitesides, G. M. & Boncheva, M. Beyond molecules: self-assembly of mesoscopic and macroscopic components. Proc. Natl Acad. Sci. USA 99, 4769–4774 (2002).

    Article  CAS  Google Scholar 

  4. Hirst, A. R. et al. High-tech applications of self-assembling supramolecular nanostructured gel-phase materials: from regenerative medicine to electronic devices. Angew. Chem. Int. Ed. 47, 8002–8018 (2008).

    Article  CAS  Google Scholar 

  5. Capito, R. M., Azevedo, H. S., Velichko, Y. S., Mata, A. & Stupp, S. I. Self-assembly of large and small molecules into hierarchically ordered sacs and membranes. Science 319, 1812–1816 (2008).

    Article  CAS  Google Scholar 

  6. Wang, Q. et al. High-water-content mouldable hydrogels by mixing clay and a dendritic molecular binder. Nature 463, 339–343 (2010).

    Article  CAS  Google Scholar 

  7. Kiyonaka, S. et al. Semi-wet peptide/protein array using supramolecular hydrogel. Nature Mater. 3, 58–64 (2004).

    Article  CAS  Google Scholar 

  8. Jonkheijm, P., van der Schoot, P., Schenning, A. P. H. J. & Meijer, E. W. Probing the solvent-assisted nucleation pathway in chemical self-assembly. Science 313, 80–83 (2006).

    Article  CAS  Google Scholar 

  9. Lloyd, G. O. & Steed, J. W. Anion-tuning of supramolecular gel properties. Nature Chem. 1, 437–442 (2009).

    Article  CAS  Google Scholar 

  10. Carnall, J. M. A. et al. Mechanosensitive self-replication driven by self-organization. Science 327, 1502–1506 (2010).

    Article  CAS  Google Scholar 

  11. Cui, H. et al. Spontaneous and X-ray triggered crystallization at long range in self-assembling filament networks. Science 327, 555–559 (2010).

    Article  CAS  Google Scholar 

  12. Winkler, S., Wilson, D. & Kaplan, D. L. Controlling β-sheet assembly in genetically engineered silk by enzymatic phosphorylation/dephosphorylation. Biochemistry 39, 12739–12746 (2000).

    Article  CAS  Google Scholar 

  13. Hu, B. H. & Messersmith, P. B. Rational design of transglutaminase substrate peptides for rapid enzymatic formation of hydrogels. J. Am. Chem. Soc. 125, 14298–14299 (2003).

    Article  CAS  Google Scholar 

  14. Yang, Z. M. et al. Enzymatic formation of supramolecular hydrogels. Adv. Mater. 16, 1440–1444 (2004).

    Article  CAS  Google Scholar 

  15. Um, S. H. et al. Enzyme-catalysed assembly of DNA hydrogel. Nature Mater. 5, 797–801 (2006).

    Article  CAS  Google Scholar 

  16. Williams, R. J. et al. Enzyme-assisted self-assembly under thermodynamic control. Nature Nanotech. 4, 19–24 (2009).

    Article  CAS  Google Scholar 

  17. Adler-Abramovich, L., Perry, R., Sagi, A., Gazit, E. & Shabat D. Controlled assembly of peptide nanotubes triggered by enzymatic activation of self-immolative dendrimers. ChemBioChem 8, 859–862 (2007).

    Article  CAS  Google Scholar 

  18. Cui, H., Chen, Z., Zhong, S., Wooley, K. L. & Pochan, D. J. Block copolymer assembly via kinetic control. Science 317, 647–650 (2007).

    Article  CAS  Google Scholar 

  19. Yamamoto, T. et al. Stabilization of a kinetically favored nanostructure: surface ROMP of self-assembled conductive nanocoils from a norbornene-appended hexa-peri-hexabenzocoronene. J. Am. Chem. Soc. 128, 14337–14340 (2006).

    Article  CAS  Google Scholar 

  20. Haines-Butterick, L. et al. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells. Proc. Natl Acad. Sci. USA 104, 7791–7796 (2007).

    Article  CAS  Google Scholar 

  21. Zhang, S. Fabrication of novel materials through molecular self-assembly. Nature Biotechnol. 21, 1171–1178 (2003).

    Article  CAS  Google Scholar 

  22. Banwell, E. F. et al. Rational design and application of responsive alpha-helical peptide hydrogels. Nature Mater. 8, 596–600 (2009).

    Article  CAS  Google Scholar 

  23. Adler-Abramovich, L. et al. Self-assembled arrays of peptide nanotubes by vapour deposition. Nature Nanotech. 4, 849–854 (2009).

    Article  CAS  Google Scholar 

  24. Smith, A. M. et al. Fmoc-diphenylalanine self assembles to a hydrogel via a novel architecture based on pi−pi interlocked beta-sheets. Adv. Mater. 20, 37–41 (2008).

    Article  CAS  Google Scholar 

  25. Zhang, Y., Gu, H., Yang, Z. & Xu, B. Supramolecular hydrogels respond to ligand−receptor interaction. J. Am. Chem. Soc. 125, 13680–13681 (2003).

    Article  CAS  Google Scholar 

  26. Keller, D. & Bustamante, C. Theory of the interaction of light with large inhomogeneous molecular aggregates. II. psi-type circular dichroism. J. Chem. Phys. 84, 2972–2980 (1986).

    Article  CAS  Google Scholar 

  27. Martin, J. E. & Wilcoxon, J. P. Critical dynamics of the sol–gel transition. Phys. Rev. Lett. 61, 373–376 (1988).

    Article  CAS  Google Scholar 

  28. Fang, L., Brown, W. & Konak, C. Dynamic light scattering study of the sol–gel transition. Macromolecules 24, 6839–6842 (1991).

    Article  CAS  Google Scholar 

  29. Weijers, M., Visschers, R. W. & Nicolai, T. Light scattering study of heat-induced aggregation and gelation of ovalbumin. Macromolecules 35, 4753–4762 (2002).

    Article  CAS  Google Scholar 

  30. Yamamoto, Y. et al. Photoconductive coaxial nanotubes of molecularly connected electron donor and acceptor Layers. Science 314, 1761–1764 (2006).

    Article  CAS  Google Scholar 

  31. Schenning, A. P. H. J. & Meijer, E. W. Supramolecular electronics; nanowires from self-assembled π-conjugated systems. Chem. Commun. 26, 3245–3258 (2005).

    Article  Google Scholar 

  32. Xu, H. et al. An investigation of the conductivity of peptide nanotube networks prepared by enzyme-triggered self-assembly. Nanoscale 2, 960–966 (2010).

    Article  CAS  Google Scholar 

  33. Ashkenasy, N., Seth Horne, W. & Ghadiri, M. R. Design of self-assembling peptide nanotubes with delocalized electronic states. Small 2, 99–102 (2006).

    Article  CAS  Google Scholar 

Download references


The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC), Human Frontiers Science Programme (HFSP) and the Leverhulme Trust (UK) for funding. The authors also thank L. Birchall and P.F. Caponi for assistance with graphics.

Author information

Authors and Affiliations



A.R.H., S.R., J.S., S.S. and R.V.U. conceived and designed the experiments. A.R.H., S.R., M.A., A.K.D., N.H., N.J. and J.B. performed the experiments. A.R.H., S.R., P.M., J.S., S.S. and R.V.U. analysed the data. S.M., J.H.v.E. and N.T.H. contributed materials/analysis tools. A.R.H., S.R., S.S. and R.V.U. co-wrote the paper.

Corresponding author

Correspondence to Rein V. Ulijn.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 1099 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hirst, A., Roy, S., Arora, M. et al. Biocatalytic induction of supramolecular order. Nature Chem 2, 1089–1094 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing