Abstract

Emergent properties of natural biomaterials result from the collective effects of nanoscale interactions among ordered and disordered domains. Here, using recombinant sequence design, we have created a set of partially ordered polypeptides to study emergent hierarchical structures by precisely encoding nanoscale order–disorder interactions. These materials, which combine the stimuli-responsiveness of disordered elastin-like polypeptides and the structural stability of polyalanine helices, are thermally responsive with tunable thermal hysteresis and the ability to reversibly form porous, viscoelastic networks above threshold temperatures. Through coarse-grain simulations, we show that hysteresis arises from physical crosslinking due to mesoscale phase separation of ordered and disordered domains. On injection of partially ordered polypeptides designed to transition at body temperature, they form stable, porous scaffolds that rapidly integrate into surrounding tissue with minimal inflammation and a high degree of vascularization. Sequence-level modulation of structural order and disorder is an untapped principle for the design of functional protein-based biomaterials.

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The authors declare that all data supporting the findings of this study are available within the manuscript and its supplementary files and are available from the authors on reasonable request.

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Change history

  • 31 October 2018

    In the version of this Article originally published, one of the authors’ names was incorrectly given as Jeffery Schaal; it should have been Jeffrey L. Schaal. This has been corrected in all versions of the Article.

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Acknowledgements

We thank K. Wang for his invaluable help with SIM imaging and E. Betzig for use of his facilities at Janelia Farms for SIM. This work was funded by the NIH through grants GM061232 to A.C. and R01NS056114 to R.V.P., by the NSF through grants from the Research Triangle MRSEC (DMR-11-21107), NSF DMFREF (DMR-1729671) to A.C., MCB-1614766 to R.V.P., and through the Graduate Research Fellowship Program under grant no. 1106401 to S.R.

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Affiliations

  1. Department of Biomedical Engineering, Duke University, Durham, NC, USA

    • Stefan Roberts
    • , Jeffrey L. Schaal
    • , Vincent Miao
    • , Andrew Hunt
    • , Yi Wen
    • , Joel H. Collier
    •  & Ashutosh Chilkoti
  2. Department of Physics, Washington University in St. Louis, St. Louis, MO, USA

    • Tyler S. Harmon
  3. Department of Biomedical Engineering and Center for Biological Systems Engineering , Washington University in St. Louis, St. Louis, MO, USA

    • Tyler S. Harmon
    •  & Rohit V. Pappu
  4. Department of Biochemistry, Duke University, Durham, NC, USA

    • Kan (Jonathan) Li
    •  & Terrence G. Oas

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Contributions

S.R. designed and performed experiments, analysed data and prepared the manuscript. T.S.H. designed and performed the coarse-grained simulations and co-developed the phenomenological model for hysteresis. J.L.S. designed, performed and analysed in vivo work. K.L. designed and performed structural characterization with NMR and CD. A.H. and V.M. constructed POPs and characterized their phase behaviour. V.M. also performed rheological experiments. Y.W. designed and aided in vivo experiments. T.O. provided guidance and analysed data for POP structural characterization. J.C. provided guidance for in vivo experiments. R.V.P. provided guidance, developed the conceptual framework for hysteresis, analysed results from the coarse-grained simulations, and contributed to preparing the manuscript. A.C. provided guidance, designed experiments and prepared the manuscript. All authors participated in discussion of the data and in editing and revising the manuscript.

Competing Interests

The authors declare no competing interests for this work.

Corresponding author

Correspondence to Ashutosh Chilkoti.

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    Supplementary Methods and Discussion, Supplementary Figures 1–23, Supplementary Tables 1–4, Supplementary References 1–19

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https://doi.org/10.1038/s41563-018-0182-6