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Responsive biomimetic networks from polyisocyanopeptide hydrogels

Nature volume 493, pages 651–655 (2013)Cite this article

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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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Figure 1: Oligo(ethylene glycol)-substituted PICs.
Figure 2: AFM analysis of polymers and gel.
Figure 3: Rheological analysis of PIC gels.
Figure 4: Stiffness of the gel versus stiffness of the constituent polymer.

References

  1. Kamm, R. D. & Mofrad, M. R. K. in Cytoskeletal Mechanics: Models and Measurements (eds Mofrad, M. R. K. & Kamm, R. D. ) Ch. 1, 1–17 (Cambridge Univ. Press, 2006)

    Book  Google Scholar 

  2. Fernández, P., Pullarkat, P. A. & Ott, A. A master relation defines the nonlinear viscoelasticity of single fibroblasts. Biophys. J. 90, 3796–3805 (2006)

    Article  ADS  Google Scholar 

  3. Fernandez-Gonzalez, R. & Zallen, J. A. Feeling the squeeze: live-cell extrusion limits cell density in epithelia. Cell 149, 965–967 (2012)

    Article  CAS  Google Scholar 

  4. Storm, C., Pastore, J. J., MacKintosh, F. C., Lubensky, T. C. & Janmey, P. A. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005)

    Article  CAS  ADS  Google Scholar 

  5. Schwartz, E., Le Gac, S., Cornelissen, J. J. L. M., Nolte, R. J. M. & Rowan, A. E. Macromolecular multi-chromophoric scaffolding. Chem. Soc. Rev. 39, 1576–1599 (2010)

    Article  CAS  Google Scholar 

  6. Cornelissen, J. J. L. M. et al. β-helical polymers from isocyanopeptides. Science 293, 676–680 (2001)

    Article  CAS  Google Scholar 

  7. Keereweer, B. et al. in Functional Supramolecular Architectures Vol. 1 (eds Samori, P. & Cacialli, F. ) Ch. 5, 135–152 (VCH, 2011)

  8. Lin, Y.-C. et al. Origins of elasticity in intermediate filament networks. Phys. Rev. Lett. 104, 058101 (2010)

    Article  ADS  Google Scholar 

  9. MacKintosh, F. C., Kas, J. & Janmey, P. A. Elasticity of semiflexible biopolymer networks. Phys. Rev. Lett. 75, 4425–4428 (1995)

    Article  CAS  ADS  Google Scholar 

  10. Gardel, M. L. et al. Elastic behavior of cross-linked and bundled actin networks. Science 304, 1301–1305 (2004)

    Article  CAS  ADS  Google Scholar 

  11. Tiller, J. C. Increasing the local concentration of drugs by hydrogel formation. Angew. Chem. Int. Edn 42, 3072–3075 (2003)

    Article  CAS  Google Scholar 

  12. Place, E. S., Evans, N. D. & Stevens, M. M. Complexity in biomaterials for tissue engineering. Nature Mater. 8, 457–470 (2009)

    Article  CAS  ADS  Google Scholar 

  13. Peppas, N. A., Hilt, J. Z., Khademhosseini, A. & Langer, R. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18, 1345–1360 (2006)

    Article  CAS  Google Scholar 

  14. Hirst, A. R., Escuder, B., Miravet, J. F. & Smith, D. K. High-tech applications of self-assembling supramolecular nanostructured gel-phase materials: from regenerative medicine to electronic devices. Angew. Chem. Int. Edn 47, 8002–8018 (2008)

    Article  CAS  Google Scholar 

  15. Rowan, A. E. et al. Method for the preparation of high molecular weight oligo(alkylene glycol) functionalized polyisocyanopeptides. European Patent 2,287,221. (2011)

  16. Grason, G. M. & Bruinsma, R. F. Chirality and equilibrium biopolymer bundles. Phys. Rev. Lett. 99, 098101 (2007)

    Article  ADS  Google Scholar 

  17. Pollard, T. D. & Cooper, J. A. Actin and actin-binding proteins — a critical evaluation of mechanisms and functions. Annu. Rev. Biochem. 55, 987–1035 (1986)

    Article  CAS  Google Scholar 

  18. Leterrier, J. F., Kas, J., Hartwig, J., Vegners, R. & Janmey, P. A. Mechanical effects of neurofilament cross-bridges — modulation by phosphorylation, lipids, and interactions with F-actin. J. Biochem. 271, 15687–15694 (1996)

    CAS  Google Scholar 

  19. Han, S., Hagiwara, M. & Ishizone, T. Synthesis of thermally sensitive water-soluble polymethacrylates by living anionic polymerizations of oligo(ethylene glycol) methyl ether methacrylates. Macromolecules 36, 8312–8319 (2003)

    Article  CAS  ADS  Google Scholar 

  20. Lutz, J. F. & Hoth, A. Preparation of ideal PEG analogues with a tunable thermosensitivity by controlled radical copolymerization of 2-(2-methoxyethoxy)ethyl methacrylate and oligo(ethylene glycol) methacrylate. Macromolecules 39, 893–896 (2006)

    Article  CAS  ADS  Google Scholar 

  21. Wang, H. et al. A structure-gelation ability study in a short peptide-based ‘Super Hydrogelator’ system. Soft Matter 7, 3897–3905 (2011)

    Article  CAS  ADS  Google Scholar 

  22. Mason, T. G., Dhople, A. & Wirtz, D. Linear viscoelastic moduli of concentrated DNA solutions. Macromolecules 31, 3600–3603 (1998)

    Article  CAS  ADS  Google Scholar 

  23. Onck, P. R., Koeman, T., van Dillen, T. & van der Giessen, E. Alternative explanation of stiffening in cross-linked semiflexible networks. Phys. Rev. Lett. 95, 178102 (2005)

    Article  CAS  ADS  Google Scholar 

  24. Huisman, E. M., van Dillen, T., Onck, P. R. & Van der Giessen, E. Three-dimensional cross-linked F-actin networks: relation between network architecture and mechanical behavior. Phys. Rev. Lett. 99, 208103 (2007)

    Article  CAS  ADS  Google Scholar 

  25. Broedersz, C. P. & MacKintosh, F. C. Molecular motors stiffen non-affine semiflexible polymer networks. Soft Matter 7, 3186–3191 (2011)

    Article  CAS  ADS  Google Scholar 

  26. Bustamante, C., Marko, J. F., Siggia, E. D. & Smith, S. Entropic elasticity of λ-phage DNA. Science 265, 1599–1600 (1994)

    Article  CAS  ADS  Google Scholar 

  27. Van Buul, A. M. et al. Stiffness versus architecture of single helical polyisocyanopeptides. Chem. Sci (submitted)

  28. Bathe, M., Heussinger, C., Claaessens, M. M. A. E., Bausch, A. R. & Frey, E. Cytoskeletal bundle mechanics. Biophys. J. 94, 2955–2964 (2008)

    Article  CAS  ADS  Google Scholar 

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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).

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Author notes

  1. Richard Hoogenboom

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

  2. Paul H. J. Kouwer and Matthieu Koepf: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Materials, Radboud University Nijmegen, Institute for Molecules and 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. Department of NanoStructured Materials, Delft University of Technology, 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.

Corresponding authors

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

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The authors declare no competing financial interests.

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Kouwer, P., Koepf, M., Le Sage, V. et al. Responsive biomimetic networks from polyisocyanopeptide hydrogels. Nature 493, 651–655 (2013). https://doi.org/10.1038/nature11839

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