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Energy landscapes and functions of supramolecular systems

Abstract

By means of two supramolecular systems—peptide amphiphiles engaged in hydrogen-bonded β-sheets, and chromophore amphiphiles driven to assemble by π-orbital overlaps—we show that the minima in the energy landscapes of supramolecular systems are defined by electrostatic repulsion and the ability of the dominant attractive forces to trap molecules in thermodynamically unfavourable configurations. These competing interactions can be selectively switched on and off, with the order of doing so determining the position of the final product in the energy landscape. Within the same energy landscape, the peptide-amphiphile system forms a thermodynamically favoured product characterized by long bundled fibres that promote biological cell adhesion and survival, and a metastable product characterized by short monodisperse fibres that interfere with adhesion and can lead to cell death. Our findings suggest that, in supramolecular systems, functions and energy landscapes are linked, superseding the more traditional connection between molecular design and function.

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Figure 1: Energy landscapes of PA self-assembly and pathways to access each well.
Figure 2: Micrographs and spectroscopic assessment of morphologies of all products.
Figure 3: Assessment of morphological transitions of PA assemblies as a function of ionic strength.
Figure 4: Implications of the thermodynamic state of PA assemblies on their cytotoxicity.
Figure 5: Implications of the thermodynamic state of PA assemblies on their bioactivity as a scaffold.

References

  1. Stupp, S. I. et al. Supramolecular materials: self-organized nanostructures. Science 276, 384–389 (1997).

    CAS  Article  Google Scholar 

  2. Bachmann, P. A., Luisi, P. L. & Lang, J. Autocatalytic self-replicating micelles as models for prebiotic structures. Nature 357, 57–59 (1992).

    CAS  Article  Google Scholar 

  3. Silva, G. A. et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibres. Science 303, 1352–1355 (2004).

    CAS  Article  Google Scholar 

  4. Boekhoven, J., Hendriksen, W. E., Koper, G. J., Eelkema, R. & van Esch, J. H. Transient assembly of active materials fueled by a chemical reaction. Science 349, 1075–1079 (2015).

    CAS  Article  Google Scholar 

  5. Aggeli, A. et al. Responsive gels formed by the spontaneous self-assembly of peptides into polymeric β-sheet tapes. Nature 386, 259–262 (1997).

    CAS  Article  Google Scholar 

  6. de Jong, J. J., Lucas, L. N., Kellogg, R. M., van Esch, J. H. & Feringa, B. L. Reversible optical transcription of supramolecular chirality into molecular chirality. Science 304, 278–281 (2004).

    CAS  Article  Google Scholar 

  7. Aida, T., Meijer, E. W. & Stupp, S. I. Functional supramolecular polymers. Science 335, 813–817 (2012).

    CAS  Article  Google Scholar 

  8. Boekhoven, J. et al. Catalytic control over supramolecular gel formation. Nature Chem. 5, 433–437 (2013).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  10. Korevaar, P. A. et al. Pathway complexity in supramolecular polymerization. Nature 481, 492–496 (2012).

    CAS  Article  Google Scholar 

  11. Korevaar, P. A., Newcomb, C. J., Meijer, E. W. & Stupp, S. I. Pathway selection in peptide amphiphile assembly. J. Am. Chem. Soc. 136, 8540–8543 (2014).

    CAS  Article  Google Scholar 

  12. Gröschel, A. H. et al. Precise hierarchical self-assembly of multicompartment micelles. Nature Commun. 3, 710 (2012).

    Article  Google Scholar 

  13. Weingarten, A. S. et al. Self-assembling hydrogel scaffolds for photocatalytic hydrogen production. Nature Chem. 6, 964–970 (2014).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  15. Tysseling-Mattiace, V. M. et al. Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury. J. Neurosci. 28, 3814–3823 (2008).

    CAS  Article  Google Scholar 

  16. Webber, M. J. et al. Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair. Proc. Natl Acad. Sci. USA 108, 13438–13443 (2011).

    CAS  Article  Google Scholar 

  17. Newcomb, C. J. et al. Cell death versus cell survival instructed by supramolecular cohesion of nanostructures. Nature Commun. 5, 3321 (2014).

    Article  Google Scholar 

  18. Goldberger, J. E., Berns, E. J., Bitton, R., Newcomb, C. J. & Stupp, S. I. Electrostatic control of bioactivity. Angew. Chem. Int. Ed. 50, 6292–6295 (2011).

    CAS  Article  Google Scholar 

  19. Cui, H. et al. Spontaneous and x-ray-triggered crystallization at long range in self-assembling filament networks. Science 327, 555–559 (2010).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  21. Smulders, M. M. et al. How to distinguish isodesmic from cooperative supramolecular polymerisation. Chemistry 16, 362–367 (2010).

    CAS  Article  Google Scholar 

  22. Lee, O. S., Stupp, S. I. & Schatz, G. C. Atomistic molecular dynamics simulations of peptide amphiphile self-assembly into cylindrical nanofibers. J. Am. Chem. Soc. 133, 3677–3683 (2011).

    CAS  Article  Google Scholar 

  23. Boekhoven, J. & Stupp, S. I. Supramolecular materials for regenerative medicine. Adv. Mater. 26, 1642–1659 (2014).

    CAS  Article  Google Scholar 

  24. Allen, T. M. & Cleland, L. G. Serum-induced leakage of liposome contents. Biochim. Biophys. Acta 597, 418–426 (1980).

    CAS  Article  Google Scholar 

  25. Xue, W. F. et al. Fibril fragmentation enhances amyloid cytotoxicity. J. Biol. Chem. 284, 34272–34282 (2009).

    CAS  Article  Google Scholar 

  26. Milanesi, L. et al. Direct three-dimensional visualization of membrane disruption by amyloid fibrils. Proc. Natl Acad. Sci. USA 109, 20455–20460 (2012).

    CAS  Article  Google Scholar 

  27. Pierschbacher, M. D. & Ruoslahti, E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309, 30–33 (1984).

    CAS  Article  Google Scholar 

  28. Boekhoven, J., Rubert Pérez, C. M., Sur, S., Worthy, A. & Stupp, S. I. Dynamic display of bioactivity through host-guest chemistry. Angew. Chem. Int. Ed. 46, 12077–12080 (2013).

    Article  Google Scholar 

  29. Prager-Khoutorsky, M. et al. Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing. Nature Cell. Biol. 13, 1457–1465 (2011).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  31. Boekhoven, J. et al. Dissipative self-assembly of a molecular gelator by using a chemical fuel. Angew. Chem. Int. Ed. 49, 4825–4828 (2010).

    CAS  Article  Google Scholar 

  32. Greenfield, N. J. Analysis of the kinetics of folding of proteins and peptides using circular dichroism. Nature Protoc. 1, 2891–2899 (2006).

    CAS  Article  Google Scholar 

  33. Sur, S., Matson, J. B., Webber, M. J., Newcomb, C. J. & Stupp, S. I. Photodynamic control of bioactivity in a nanofiber matrix. ACS Nano 6, 10776–10785 (2012).

    CAS  Article  Google Scholar 

  34. Wang, X. et al. Nano-biomechanical study of spatio-temporal cytoskeleton rearrangements that determine subcellular mechanical properties and endothelial permeability. Sci. Rep. 5, 11097 (2015).

    CAS  Article  Google Scholar 

  35. Meijering, E., Dzyubachyk, O. & Smal, I. Methods for cell and particle tracking. Methods Enzymol. 504, 183–200 (2012).

    Article  Google Scholar 

Download references

Acknowledgements

Synthesis of PAs, their morphological assessments, MD simulations and free energy calculations were supported by the Center for Bio-Inspired Energy Sciences (CBES), an Energy Frontiers Research Center (EFRC) funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under award number DE-SC0000989. The biological studies were supported by National Institutes of Health NIDCR grant (R01DE015920). J.B., F.T. and J.L. are grateful for support by a Rubicon Fellowship of the Netherlands Organisation for Scientific Research (NWO), the Royal Thai Government scholarship and the Northwestern University Bioscientist Program, respectively. We acknowledge the following core facilities at Northwestern University: the Peptide Synthesis Core at the Simpson Querrey Institute for BioNanotechnology, the Biological Imaging Facility (supported by the Northwestern University Office for Research), the Center for Advanced Microscopy (NCI CCSG P30 CA060553), Keck Biophysics Facility, the EPIC, SPID facility (NUANCE Center- NSF DMR-1121262 and NSF EEC-0647560). The authors thank M. Seniw for help with graphics.

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F.T. and J.B. designed and performed experiments, analysed data, and wrote the manuscript. X.W., R.V.K., G.S.S., E.Z., R.Z., C.J.N., J.H.O., J.L. and L.C.P. performed experiments, analysed data and took part in discussions. T.Y., G.C.S. and M.O.d.l.C. developed and performed theoretical calculations and took part in discussions. S.I.S. wrote the manuscript and supervised the research.

Corresponding author

Correspondence to Samuel I. Stupp.

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Tantakitti, F., Boekhoven, J., Wang, X. et al. Energy landscapes and functions of supramolecular systems. Nature Mater 15, 469–476 (2016). https://doi.org/10.1038/nmat4538

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