Abstract

Mechanical responsiveness is essential to all biological systems down to the level of tissues and cells1,2. The intra- and extracellular mechanics of such systems are governed by a series of proteins, such as microtubules, actin, intermediate filaments and collagen3,4. As a general design motif, these proteins self-assemble into helical structures and superstructures that differ in diameter and persistence length to cover the full mechanical spectrum1. Gels of cytoskeletal proteins display particular mechanical responses (stress stiffening) that until now have been absent in synthetic polymeric and low-molar-mass gels. Here we present synthetic gels that mimic in nearly all aspects gels prepared from intermediate filaments. They are prepared from polyisocyanopeptides5,6,7 grafted with oligo(ethylene glycol) side chains. These responsive polymers possess a stiff and helical architecture, and show a tunable thermal transition where the chains bundle together to generate transparent gels at extremely low concentrations. Using characterization techniques operating at different length scales (for example, macroscopic rheology, atomic force microscopy and molecular force spectroscopy) combined with an appropriate theoretical network model8,9,10, we establish the hierarchical relationship between the bulk mechanical properties and the single-molecule parameters. Our results show that to develop artificial cytoskeletal or extracellular matrix mimics, the essential design parameters are not only the molecular stiffness, but also the extent of bundling. In contrast to the peptidic materials, our polyisocyanide polymers are readily modified, giving a starting point for functional biomimetic hydrogels with potentially a wide variety of applications11,12,13,14, in particular in the biomedical field.

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Acknowledgements

We thank B. Norder for assistance with rheological experiments, C. Broersz for support with nonlinear rheology, F. MacKintosh for discussions on the interpretation of the semi-flexible polymer network theory and E. Cator for work on the statistical analysis of the AFM images. We acknowledge financial support from Technology Foundation STW, the Council for the Chemical Sciences of the Netherlands Organisation for Scientific Research (NWO-CW-7005644), NRSCC, the Royal Academy for Arts and Sciences and EU projects Hierarchy (PITN-CT-2007-215851) and Superior (PITN-CT-2009-238177).

Author information

Author notes

    • Paul H. J. Kouwer
    •  & Matthieu Koepf

    These authors contributed equally to this work.

    • Richard Hoogenboom

    Present address: Supramolecular Chemistry Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Ghent, Belgium.

Affiliations

  1. Radboud University Nijmegen, Institute for Molecules and Materials, Department of Molecular Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands

    • Paul H. J. Kouwer
    • , Matthieu Koepf
    • , Vincent A. A. Le Sage
    • , Maarten Jaspers
    • , Arend M. van Buul
    • , Zaskia H. Eksteen-Akeroyd
    • , Tim Woltinge
    • , Erik Schwartz
    • , Heather J. Kitto
    • , Richard Hoogenboom
    • , Roeland J. M. Nolte
    •  & Alan E. Rowan
  2. Delft University of Technology, Department of NanoStructured Materials, Julianalaan 136, 2628 BL Delft, The Netherlands

    • Stephen J. Picken
    •  & Eduardo Mendes

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Contributions

P.H.J.K. and A.E.R. wrote the manuscript and developed the model. M.K, Z.H.E.-A., T.W., E.S., H.J.K. and R.H. were involved in the design, synthesis and characterization of the materials. M.J. and A.M.v.B. conducted the SMFS measurements. V.A.A.L.S., P.H.J.K., E.M. and S.J.P. designed, conducted and interpreted the rheological experiment. P.H.J.K., R.J.M.N. and A.E.R. supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Paul H. J. Kouwer or Alan E. Rowan.

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    Supplementary Information

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DOI

https://doi.org/10.1038/nature11839

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