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Peptide tessellation yields micrometre-scale collagen triple helices

Nature Chemistry volume 8, pages 1008–1014 (2016)Cite this article

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Abstract

Sticky-ended DNA duplexes can associate spontaneously into long double helices; however, such self-assembly is much less developed with proteins. Collagen is the most prevalent component of the extracellular matrix and a common clinical biomaterial. As for natural DNA, the ~103-residue triple helices (~300 nm) of natural collagen are recalcitrant to chemical synthesis. Here we show how the self-assembly of short collagen-mimetic peptides (CMPs) can enable the fabrication of synthetic collagen triple helices that are nearly a micrometre in length. Inspired by the mathematics of tessellations, we derive rules for the design of single CMPs that self-assemble into long triple helices with perfect symmetry. Sticky ends thus created are uniform across the assembly and drive its growth. Enacting this design yields individual triple helices that, in length, match or exceed those in natural collagen and are remarkably thermostable, despite the absence of higher-order association. The symmetric assembly of CMPs provides an enabling platform for the development of advanced materials for medicine and nanotechnology.

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Figure 1: Design of symmetric CMP self-assemblies.
Figure 2: Characterization of 4sb-derived CMP self-assemblies.
Figure 3: Perturbing the strand-association landscape abolishes assembly.
Figure 4: Benefits of symmetric assembly.

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Acknowledgements

We thank A. J. Ellison, B. M. Hoover, R. Biswas and S. Chattopadhyay for help with solution- and solid-phase peptide synthesis, S. A. Morin for help with nanocharacterization, M. D. Shoulders, F. W. Kotch and E. Emrah for discussions on the CMP assembly and R. W. Newberry for reviewing the manuscript. This study would not have been possible without expert advice and assistance from M. D. Boersma and N. Porcaro (UW Biotechnology Center) and from D. R. McCaslin (UW BIF). A.F. and S.J. were supported by Grant DMR-0832760 (National Science Foundation). This work was supported by Grant R01 AR044276 (National Institutes of Health).

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Authors and Affiliations

  1. Department of Biochemistry, University of Wisconsin–Madison, Madison, 53706, Wisconsin, USA

    I. Caglar Tanrikulu & Ronald T. Raines

  2. Department of Chemistry, University of Wisconsin–Madison, Madison, 53706, Wisconsin, USA

    Audrey Forticaux, Song Jin & Ronald T. Raines

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  1. I. Caglar Tanrikulu
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Contributions

I.C.T and R.T.R. conceived the project and planned the experiments. I.C.T. designed, synthesized and characterized the peptides in solution, and computed their association landscapes. A.F. imaged the peptide assemblies. All the authors analysed the data. I.C.T. and R.T.R. wrote the paper. All the authors proofread, commented on and approved the manuscript.

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Correspondence to Ronald T. Raines.

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Tanrikulu, I., Forticaux, A., Jin, S. et al. Peptide tessellation yields micrometre-scale collagen triple helices. Nature Chem 8, 1008–1014 (2016). https://doi.org/10.1038/nchem.2556

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