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Energy landscapes and functions of supramolecular systems


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.


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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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Authors and Affiliations



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.

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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).

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