Living supramolecular polymerization realized through a biomimetic approach


Various conventional reactions in polymer chemistry have been translated to the supramolecular domain, yet it has remained challenging to devise living supramolecular polymerization. To achieve this, self-organization occurring far from thermodynamic equilibrium—ubiquitously observed in nature—must take place. Prion infection is one example that can be observed in biological systems. Here, we present an ‘artificial infection’ process in which porphyrin-based monomers assemble into nanoparticles, and are then converted into nanofibres in the presence of an aliquot of the nanofibre, which acts as a ‘pathogen’. We have investigated the assembly phenomenon using isodesmic and cooperative models and found that it occurs through a delicate interplay of these two aggregation pathways. Using this understanding of the mechanism taking place, we have designed a living supramolecular polymerization of the porphyrin-based monomers. Despite the fact that the polymerization is non-covalent, the reaction kinetics are analogous to that of conventional chain growth polymerization, and the supramolecular polymers were synthesized with controlled length and narrow polydispersity.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Formation and transformation of supramolecular assembly of 1.
Figure 2: Kinetic and thermodynamic studies of the self-assembly behaviour of 1.
Figure 3: Kinetic studies of supramolecular polymerization initiated upon addition of H-aggregate seeds (1H-seed).
Figure 4: Living supramolecular polymerization of 1.
Figure 5: Polymer propagation from the termini of the 1H-seed seeds on a silicon substrate.


  1. 1

    Brunsveld, L., Folmer, B. J. B., Meijer, E. W. & Sijbesma, R. P. Supramolecular polymers. Chem. Rev. 101, 4071–4097 (2001).

    CAS  PubMed  Google Scholar 

  2. 2

    Aida, T., Meijer, E. W. & Stupp, S. I. Functional supramolecular polymers. Science 335, 813–817 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Hoeben, F. J. M., Jonkheijm, P., Meijer, E. W. & Schenning, A. P. H. J. About supramolecular assemblies of π-conjugated systems. Chem. Rev. 105, 1491–1546 (2005).

    CAS  PubMed  Google Scholar 

  4. 4

    Elemans, J. A. A. W., van Hameren, R., Nolte, R. J. M. & Rowan, A. E. Molecular materials by self-assembly of porphyrins, phthalocyanines, and perylenes. Adv. Mater. 18, 1251–1266 (2006).

    CAS  Google Scholar 

  5. 5

    Wu, J., Pisula, W. & Müllen, K. Graphenes as potential material for electronics. Chem. Rev. 107, 718–747 (2007).

    CAS  PubMed  Google Scholar 

  6. 6

    Ajayaghosh, A., Praveen, V. K. & Vijayakumar, C. Organogels as scaffolds for excitation energy transfer and light harvesting. Chem. Soc. Rev. 37, 109–122 (2008).

    CAS  PubMed  Google Scholar 

  7. 7

    Rosen, B. M. et al. Dendron-mediated self-assembly, disassembly, and self-organization of complex systems. Chem. Rev. 109, 6275–6540 (2009).

    CAS  PubMed  Google Scholar 

  8. 8

    Martin, R. B. Comparisons of indefinite self-association models. Chem. Rev. 96, 3043–3064 (1996).

    CAS  PubMed  Google Scholar 

  9. 9

    Zhao, D. & Moore, J. S. Nucleation–elongation: a mechanism for cooperative supramolecular polymerization. Org. Biomol. Chem. 1, 3471–3491 (2003).

    CAS  PubMed  Google Scholar 

  10. 10

    De Greef, T. F. A. et al. Supramolecular polymerization. Chem. Rev. 109, 5687–5754 (2009).

    CAS  PubMed  Google Scholar 

  11. 11

    Chen, Z., Lohr, A., Saha-Möller, C. R. & Würthner, F. Self-assembled π-stacks of functional dyes in solution: structural and thermodynamic features. Chem. Soc. Rev. 38, 564–584 (2009).

    CAS  PubMed  Google Scholar 

  12. 12

    Chen, Z. et al. Photoluminescence and conductivity of self-assembled π–π stacks of perylene bisimide dyes. Chem. Eur. J. 13, 436–449 (2007).

    CAS  PubMed  Google Scholar 

  13. 13

    Smulders, M. M. J. et al. How to distinguish isodesmic from cooperative supramolecular polymerisation. Chem. Eur. J. 16, 362–367 (2010).

    CAS  PubMed  Google Scholar 

  14. 14

    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).

    CAS  Google Scholar 

  15. 15

    Smulders, M. M. J., Schenning, A. P. H. J. & Meijer E. W. Insight into the mechanisms of cooperative self-assembly: the ‘sergeants-and-soldiers’ principle of chiral and achiral C3-symmetrical discotic triamides. J. Am. Chem. Soc. 130, 606–611 (2008).

    CAS  PubMed  Google Scholar 

  16. 16

    Fernández, G., Stolte, M., Stepanenko, V. & Würthner, F. Cooperative supramolecular polymerization: comparison of different models applied on the self-assembly of bis(merocyanine) dyes. Chem. Eur. J. 19, 206–217 (2013).

    PubMed  Google Scholar 

  17. 17

    Odian, G. Principles of Polymerization 4th edn (Wiley, 2004).

    Google Scholar 

  18. 18

    Khuong, K. S., Jones, W. H., Pryor, W. A. & Houk, K. N. The mechanism of the self-initiated thermal polymerization of styrene. Theoretical solution of a classic problem. J. Am. Chem. Soc. 127, 1265–1277 (2005).

    CAS  PubMed  Google Scholar 

  19. 19

    Breslow, R. Biomimetic chemistry: biology as an inspiration. J. Biol. Chem. 284, 1337–1342 (2009).

    CAS  Google Scholar 

  20. 20

    Alper, T., Cramp, W. A., Haig, D. A. & Clarke, M. C. Does the agent of scrapie replicate without nucleic acid? Nature 214, 764–766 (1967).

    CAS  PubMed  Google Scholar 

  21. 21

    Griffith, J. S. Self-replication and scrapie. Nature 215, 1043–1044 (1967).

    CAS  PubMed  Google Scholar 

  22. 22

    Laurent, M. Prion diseases and the ‘protein only’ hypothesis: a theoretical dynamic study. Biochem. J. 318, 35–39 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Aguzzi, A. & Calella, A. M. Prions: protein aggregation and infectious diseases. Physiol. Rev. 89, 1105–1152 (2009).

    CAS  Google Scholar 

  24. 24

    Korevaar, P. A. et al. Pathway complexity in supramolecular polymerization. Nature 481, 492–496 (2012).

    CAS  PubMed  Google Scholar 

  25. 25

    Van Hameren, R. et al. Macroscopic hierarchical surface patterning of porphyrin trimers via self-assembly and dewetting. Science 314, 1433–1436 (2006).

    CAS  PubMed  Google Scholar 

  26. 26

    Helmich, F. et al. Dilution-induced self-assembly of porphyrin aggregates: a consequence of coupled equilibria. Angew. Chem. Int. Ed. 49, 3939–3942 (2010).

    CAS  Google Scholar 

  27. 27

    Shirakawa, M., Kawano, S., Fujita, N., Sada, K. & Shinkai, S. Hydrogen-bond-assisted control of H versus J aggregation mode of porphyrins stacks in an organogel system. J. Org. Chem. 68, 5037–5044 (2003).

    CAS  PubMed  Google Scholar 

  28. 28

    Bachmann, P. A., Luisi, P. L. & Lang, J. Autocatalytic self-replicating micelles as models for prebiotic structures. Nature 357, 57–59 (1992).

    CAS  Google Scholar 

  29. 29

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

    CAS  Google Scholar 

  30. 30

    Cheng, P-N., Liu, C., Zhao, M., Eisenberg, D. & Nowick, J. S. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity. Nature Chem. 4, 927–933 (2012).

    CAS  Google Scholar 

  31. 31

    Baskakov, I. V., Legname, G., Baldwin, M. A., Prusiner, S. B. & Cohen, F. E. Pathway complexity of prion protein assembly into amyloid. J. Biol. Chem. 277, 21140–21148 (2002).

    CAS  PubMed  Google Scholar 

  32. 32

    Baldwin, R. L. On-pathway versus off-pathway folding intermediates. Folding Des. 1, R1–lR8 (1996).

    CAS  Google Scholar 

  33. 33

    Stals, P. J. M. et al. Symmetry breaking in the self-assembly of partially fluorinated benzene-1,3,5-tricarboxamides. Angew. Chem. Int. Ed. 51, 11297–11301 (2012).

    CAS  Google Scholar 

  34. 34

    Lohr, A., Lysetska, M. & Würthner, F. Supramolecular stereomutation in kinetic and thermodynamic self-assembly of helical merocyanine dye nanorods. Angew. Chem. Int. Ed. 44, 5071–5074 (2005).

    CAS  Google Scholar 

  35. 35

    Lohr, A. & Würthner, F. Evolution of homochiral helical dye assemblies: involvement of autocatalysis in the ‘majority-rules’ effect. Angew. Chem. Int. Ed. 47, 1232–1236 (2008).

    CAS  Google Scholar 

  36. 36

    Powers, E. T. & Powers, D. L. Mechanisms of protein fibril formation: nucleated polymerization with competing off-pathway aggregation. Biophys. J. 94, 379–391 (2008).

    CAS  PubMed  Google Scholar 

  37. 37

    Wang, X. et al. Cylindrical block copolymer micelles and co-micelles of controlled length and architecture. Science 317, 644–647 (2007).

    CAS  PubMed  Google Scholar 

  38. 38

    Gädt, T. et al. Complex and hierarchical micelle architectures from diblock copolymers using living, crystallization-driven polymerizations. Nature Mater. 8, 144–150 (2009).

    Google Scholar 

  39. 39

    Gilroy, J. B. et al. Monodisperse cylindrical micelles by crystallization-driven living self-assembly. Nature Chem. 2, 566–570 (2010).

    CAS  Google Scholar 

  40. 40

    Qiu, H. et al. Tunable supermicelle architectures from the hierarchical self-assembly of amphiphilic cylindrical B–A–B triblock co-micelles. Angew. Chem. Int. Ed. 51, 11882–11885 (2012).

    CAS  Google Scholar 

  41. 41

    Rupar. P. A., Chabanne, L., Winnik, M. A. & Manners. I. Non-centrosymmetric cylindrical micelles by unidirectional growth. Science 337, 559–562 (2012).

    CAS  PubMed  Google Scholar 

  42. 42

    Zhang, W. et al. Supramolecular linear heterojunction composed of graphite-like semiconducting nanotubular segments. Science 334, 340–343 (2011).

    CAS  PubMed  Google Scholar 

  43. 43

    George, S. J. et al. Asymmetric noncovalent synthesis of self-assembled one-dimensional stacks by a chiral supramolecular auxiliary approach. J. Am. Chem. Soc. 134, 17789–17796 (2012).

    CAS  PubMed  Google Scholar 

  44. 44

    Zhang, W., Jin, W., Fukushima, T., Ishii, N. & Aida, T. Dynamic or nondynamic? Helical trajectory in hexabenzocoronene nanotubes biased by a detachable chiral auxiliary. J. Am. Chem. Soc. 135, 114–117 (2013).

    CAS  PubMed  Google Scholar 

  45. 45

    Shao, C., Stolte, M. & Würthner, F. Quadruple π stack of two perylene bisimide tweezers: a bimolecular complex with kinetic stability. Angew. Chem. Int. Ed. 52, 7482–7486 (2013).

    CAS  Google Scholar 

  46. 46

    Shao, C., Stolte, M. & Würthner, F. Backbone-directed perylene dye self-assembly into oligomer stacks. Angew. Chem. Int. Ed. 52, 10463–10467 (2013).

    CAS  Google Scholar 

  47. 47

    Ajayaghosh, A., Varghese, R., Praveen, V. K. & Mahesh, S. Evolution of nano- to microsized spherical assemblies of a short oligo(p-phenyleneethynylene) into suprastructured organogels. Angew. Chem. Int. Ed. 45, 3261–3264 (2006).

    CAS  Google Scholar 

  48. 48

    Pashuck, E. T. & Stupp, S. I. Direct observation of morphological tranformation from twisted ribbons into helical ribbons. J. Am. Chem. Soc. 132, 8819–8821 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Smulders, M. M. J. et al. Cooperative two-component self-assembly of mono- and ditopic monomers. Macromolecules 44, 6581–6587 (2011).

    CAS  Google Scholar 

Download references


This work was supported by a Grants-in-Aid for Scientific Research (KAKENHI; no. 20750097), the Scientific Research for Priority Area ‘Coordination Programming’ (area 2107) and the Nanotechnology Network Project from the Ministry of Education, Culture, Sports, Science and Technology, Government of Japan.

Author information




K.S. conceived and directed the project. K.S. and S.M. initiated the project. S.O. carried out most of the experimental work. S.S. analysed the DLS results. S.O. and K.S. co-wrote the manuscript. S.O., K.S. and M.T. discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Kazunori Sugiyasu or Masayuki Takeuchi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 6824 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ogi, S., Sugiyasu, K., Manna, S. et al. Living supramolecular polymerization realized through a biomimetic approach. Nature Chem 6, 188–195 (2014).

Download citation

Further reading


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