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Co-assembly, spatiotemporal control and morphogenesis of a hybrid protein–peptide system

Nature Chemistry volume 7, pages 897–904 (2015)Cite this article

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Abstract

Controlling molecular interactions between bioinspired molecules can enable the development of new materials with higher complexity and innovative properties. Here we report on a dynamic system that emerges from the conformational modification of an elastin-like protein by peptide amphiphiles and with the capacity to access, and be maintained in, non-equilibrium for substantial periods of time. The system enables the formation of a robust membrane that displays controlled assembly and disassembly capabilities, adhesion and sealing to surfaces, self-healing and the capability to undergo morphogenesis into tubular structures with high spatiotemporal control. We use advanced microscopy along with turbidity and spectroscopic measurements to investigate the mechanism of assembly and its relation to the distinctive membrane architecture and the resulting dynamic properties. Using cell-culture experiments with endothelial and adipose-derived stem cells, we demonstrate the potential of this system to generate complex bioactive scaffolds for applications such as tissue engineering.

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Figure 1: Self-assembly, dynamic properties and architecture of the hybrid ELP5/PAK3 system.
Figure 2: Molecular interactions and composition of the ELP5/PAK3 membrane.
Figure 3: Relation between the molecular mechanism, membrane architecture and properties of the ELP5/PAK3 system.
Figure 4: Application in tissue engineering.

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References

  1. Sasai, Y. Cytosystems dynamics in self-organization of tissue architecture. Nature 493, 318–326 (2013).

    Article  CAS  Google Scholar 

  2. Whitesides, G. M. & Grzybowski, B. Self-assembly at all scales. Science 295, 2418–2421 (2002).

    Article  CAS  Google Scholar 

  3. Silva, N. C. S. et al. Protein-based materials: from sources to innovative sustainable materials for biomedical applications. J. Mater. Chem. B 2, 3715–3740 (2014).

    Article  CAS  Google Scholar 

  4. Urry, D. W. et al. in Biotechnological Polymers: Medical, Pharmaceutical and Industrial Applications (ed. Gebelein, C. G.) 82–103 (Technomic, 1993).

  5. Smits, F. C., Buddingh, B. C., van Eldijk, M. B. & van Hest, J. C. Elastin-like polypeptide based nanoparticles: design rationale toward nanomedicine. Macromol. Biosci. 15, 36–51 (2015).

    Article  CAS  Google Scholar 

  6. Almine, J. F. et al. Elastin-based materials. Chem. Soc. Rev. 39, 3371–3379 (2010).

    Article  CAS  Google Scholar 

  7. Martin, L., Castro, E., Ribeiro, A., Alonso, M. & Rodriguez-Cabello, J. C. Temperature-triggered self-assembly of elastin-like block co-recombinamers: the controlled formation of micelles and vesicles in an aqueous medium. Biomacromolecules 13, 293–298 (2012).

    Article  CAS  Google Scholar 

  8. Rodriguez-Cabello, J. C., Prieto, S., Reguera, J., Arias, F. J. & Ribeiro, A. Biofunctional design of elastin-like polymers for advanced applications in nanobiotechnology. J. Biomater. Sci. Polym. Ed. 18, 269–286 (2007).

    Article  CAS  Google Scholar 

  9. Fletcher, J. M. et al. Self-assembling cages from coiled-coil peptide modules. Science 340, 595–599 (2013).

    Article  CAS  Google Scholar 

  10. Tang, T.-Y. et al. Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model. Nature Chem. 6, 527–533 (2014).

    Article  Google Scholar 

  11. Hartgerink, J. D., Beniash, E. & Stupp, S. I. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294, 1684–1688 (2001).

    Article  CAS  Google Scholar 

  12. Zhang, S. et al. A self-assembly pathway to aligned monodomain gels. Nature Mater. 9, 594–601 (2010).

    Article  CAS  Google Scholar 

  13. Glaab, F., Kellermeier, M., Kunz, W., Morallon, E. & Garcia-Ruiz, J. M. Formation and evolution of chemical gradients and potential differences across self-assembling inorganic membranes. Angew. Chem. Int. Ed. 51, 4317–4321 (2012).

    Article  CAS  Google Scholar 

  14. Ritchie, C. et al. Spontaneous assembly and real-time growth of micrometre-scale tubular structures from polyoxometalate-based inorganic solids. Nature Chem. 1, 47–52 (2009).

    Article  CAS  Google Scholar 

  15. Noorduin, W. L., Grinthal, A., Mahadevan, L. & Aizenberg, J. Rationally designed complex, hierarchical microarchitectures. Science 340, 832–837 (2013).

    Article  CAS  Google Scholar 

  16. Galland, R. et al. Fabrication of three-dimensional electrical connections by means of directed actin self-organization. Nature Mater. 12, 416–421 (2013).

    Article  CAS  Google Scholar 

  17. Adler-Abramovich, L. et al. Self-assembled arrays of peptide nanotubes by vapour deposition. Nature Nanotech. 4, 849–854 (2009).

    Article  CAS  Google Scholar 

  18. Capito, R. M., Azevedo, H. S., Velichko, Y. S., Mata, A. & Stupp, S. I. Self-assembly of large and small molecules into hierarchically ordered sacs and membranes. Science 319, 1812–1816 (2008).

    Article  CAS  Google Scholar 

  19. Ferreira, D. S., Marques, A. P., Reis, R. L. & Azevedo, H. S. Hyaluronan and self-assembling peptides as building blocks to reconstruct the extracellular environment in skin tissue. Biomater. Sci. 1, 952–964 (2013).

    Article  CAS  Google Scholar 

  20. Carvajal, D. et al. Physical properties of hierarchically ordered self-assembled planar and spherical membranes. Soft Matter 6, 1816–1823 (2010).

    Article  CAS  Google Scholar 

  21. Chow, L. W. et al. A bioactive self-assembled membrane to promote angiogenesis. Biomaterials 32, 1574–1582 (2011).

    Article  CAS  Google Scholar 

  22. Velichko, Y. S. et al. Electric field controlled self-assembly of hierarchically ordered membranes. Adv. Funct. Mater. 22, 369–377 (2012).

    Article  CAS  Google Scholar 

  23. Carew, D. B., Channon, K. J., Manners, I. & Woolfson, D. N. Polyelectrolite-surfactant nanocomposite membranes formed at liquid-liquid interface. Soft Matter 7, 3475–3481 (2011).

    Article  CAS  Google Scholar 

  24. Urry, D. W. Physical chemistry of biological free energy transduction as demonstrated by elastin protein-based polymers. J. Phys. Chem. B 101, 11007–11028 (1997).

    Article  CAS  Google Scholar 

  25. Miller, R. et al. Dynamics of protein and mixed protein/surfactant adsorption layers at the water/fluid interface. Adv. Colloid Interface Sci. 86, 39–82 (2000).

    Article  CAS  Google Scholar 

  26. Kotsmar, Cs et al. Thermodynamics, adsorption kinetics and rheology of mixed protein–surfactant interfacial layers. Adv. Colloid Interface Sci. 150, 41–54 (2009).

    Article  CAS  Google Scholar 

  27. Bitton, R. et al. Electrostatic control of structure in self-assembled membranes. Small 10, 500–505 (2014).

    Article  CAS  Google Scholar 

  28. Boekhoven, J. et al. Alginate–peptide amphiphile core–shell microparticles as a targeted drug delivery system. RSC Adv. 5, 8753–8756 (2015).

    Article  CAS  Google Scholar 

  29. Mertens, H. D. & Svergun, D. I. Structural characterization of proteins and complexes using small-angle X-ray solution scattering. J. Struct. Biol. 172, 128–141 (2010).

    Article  CAS  Google Scholar 

  30. Giehm, L., Oliveira, C. L., Christiansen, G., Pedersen, J. S. & Otzen, D. E. SDS-induced fibrillation of alpha-synuclein: an alternative fibrillation pathway. J. Mol. Biol. 401, 115–133 (2010).

    Article  CAS  Google Scholar 

  31. Andersen, K. K. et al. The role of decorated SDS micelles in sub-CMC protein denaturation and association. J. Mol. Biol. 391, 207–226 (2009).

    Article  CAS  Google Scholar 

  32. Mann, S. Self-assembly and transformation of hybrid nano-objects and nanostructures under equilibrium and non-equilibrium conditions. Nature Mater. 8, 781–792 (2009).

    Article  CAS  Google Scholar 

  33. Meinhardt, H. & Gierer, A. Pattern formation by local self-activation and lateral inhibition. Bioessays 22, 753–760 (2000).

    Article  CAS  Google Scholar 

  34. Kawska, A. et al. How actin network dynamics control the onset of actin-based motility. Proc. Natl Acad. Sci. USA 109, 14440–14445 (2012).

    Article  CAS  Google Scholar 

  35. Siton, O. et al. Cortactin releases the brakes in actin-based motility by enhancing WASP-VCA detachment from Arp2/3 branches. Curr. Biol. 21, 2092–2097 (2011).

    Article  CAS  Google Scholar 

  36. Bernheim-Groswasser, A., Wiesner, S., Golsteyn, R. M., Carlier, M. F. & Sykes, C. The dynamics of actin-based motility depend on surface parameters. Nature 417, 308–311 (2002).

    Article  CAS  Google Scholar 

  37. Hirst, A. R. et al. Biocatalytic induction of supramolecular order. Nature Chem. 2, 1089–1094 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  39. Boccafoschi, F. et al. Human elastin polypeptides improve the biomechanical properties of three-dimensional matrices through the regulation of elastogenesis. J. Biomed. Mater. Res. A 103, 1218–1230 (2015).

    Article  Google Scholar 

  40. Choi, S. K., Park, J. K., Lee, K. M., Lee, S. K. & Jeon, W. B. Improved neural progenitor cell proliferation and differentiation on poly(lactide-co-glycolide) scaffolds coated with elastin-like polypeptide. J. Biomed. Mater. Res. B 101, 1329–1339 (2013).

    Article  Google Scholar 

  41. McClendon, M. T. & Stupp, S. I. Tubular hydrogels of circumferentially aligned nanofibers to encapsulate and orient vascular cells. Biomaterials 33, 5713–5722 (2012).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The work was supported by the European Research Council Starting Grant (STROFUNSCAFF), the European Commission under FP7 and H2020 programs ((NMP3-LA-2011-263363, HEALTH-F4-2011-278557, PITN-GA-2012-317304, MSCA-ITN-2014-ETN- 642687, 642687 H2020-NMP-2014-646075), the Ministry of Economy and Competitiveness (Spain) (MAT2012-38043-C02-01, MAT2013-41723-R, MAT2013-42473-R) the Junta de Castilla y Leon (VA244U13, VA313U14) and the Portuguese Foundation for Science and Technology, grants PTDC/EBB-BIO/114523/2009 and SFRH/BD/44977/2008. Additional support was obtained from the Bilateral Program Portugal–Spain Integrated Actions 2011 (E-50/11) and Marie Curie Career Integration Grant 618335. The authors thank the European Synchrotron Research Facility for access to synchrotron beamline BM29 and P. Pernot for support during the experiments, and C. López (Centres Científics i Tecnològics University of Barcelona), C. Semino (Institut Químic de Sarrià), E. Rebollo (Advanced Fluorescence Microscopy Unit in the Molecular Biology Institute of Barcelona), J. P. Aguilar, R. Doodkorte, A. Amzour and the technical staff of the Material Characterization Laboratory and Nanovision Laboratory at the Queen Mary University of London for the constructive discussions and contributions in this study.

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Authors and Affiliations

  1. School of Engineering & Materials Science, Queen Mary University of London, London, E1 4NS, UK

    Karla E. Inostroza-Brito, Estelle Collin, Daniela S. Ferreira, Lorenzo Botto, Helena S. Azevedo & Alvaro Mata

  2. Nanotechnology Platform, Parc Científic de Barcelona, Barcelona, 08028, Spain

    Karla E. Inostroza-Brito, Katherine H. Smith, Amàlia Monge-Marcet, Raúl Pérez Rodríguez & Alvaro Mata

  3. Department of Chemical Engineering and the Ilze Katz, Institute for Nanoscale Science & Technology Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel

    Orit Siton-Mendelson & Ronit Bitton

  4. 3B's Research Group – Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães, 4805-017, Portugal

    Daniela S. Ferreira, Rui L. Reis & Helena S. Azevedo

  5. ICVS/3B's, PT Government Associate Laboratory, Guimarães, 4805-017, Portugal

    Daniela S. Ferreira, Rui L. Reis & Helena S. Azevedo

  6. BIOFORGE Group, University of Valladolid, CIBER-BBN, Valladolid, 47011, Spain

    Matilde Alonso & José Carlos Rodríguez-Cabello

  7. Departament de Química Física, Universitat de Barcelona, Barcelona, 08028, Spain

    Francesc Sagués

  8. Institute of Bioengineering, Queen Mary University of London, London, E1 4NS, UK

    Lorenzo Botto, Helena S. Azevedo & Alvaro Mata

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  1. Karla E. Inostroza-Brito
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Contributions

A.M., K.H.S. and K.E.I. conceived the project. D.S.F. and H.S.A. performed the synthesis and chemical characterization of some PAs used in this study. E.C. carried out cell-culture studies. O.S and R.B. collected and analysed SAXS data. R.P.R. performed and analysed the TOF-SIM experiments and K.E.I. performed experiments. M.A., J.C.R. and R.L.R. provided facilities to perform experiments. A.M., K.E.I., A.M.-M., H.S.A., L.B., R.B. and F.S. interpreted the data and wrote the manuscript. All the authors discussed the results and commented on the manuscript.

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Correspondence to Alvaro Mata.

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The authors declare no competing financial interests.

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Inostroza-Brito, K., Collin, E., Siton-Mendelson, O. et al. Co-assembly, spatiotemporal control and morphogenesis of a hybrid protein–peptide system. Nature Chem 7, 897–904 (2015). https://doi.org/10.1038/nchem.2349

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