kinetic control of the self-assembly of (poly)peptides into 2- and 3-dimensional assemblies for hierarchical ordering of inorganic nanoparticles
Final Report Abstract
To summarize, this project could show for the first time that it is possible to computationally design denovo (poly)peptides that show a large versatility and robustness with respect to their SA into 2D lattices in aqueous solution. We could demonstrate that the peptides self-assemble into a variety of different symmetries depending on the initial display. Furthermore, the overall shape of the arrays derived from SA from a single peptide can be influenced by simply changing the pH of the aqueous solution, e.g. for sequence P222_1 and P222_9. The analysis by high-resolution TEM and small-angle X-ray scattering revealed that the d-spacings observed are in general larger as predicted by theory and calculations. First investigations in this direction point towards a relaxation of the lattice into closely related symmetries with less symmetry elements. For this purpose, crystal growth experiments for single crystal peptide X-ray crystallography are under way. Hopefully, upon solving the lattice parameters and symmetry we will soon be able solve the issue of deviating space groups between theory and experiment. It will also help to assign the preferential growth directions to changes in the protonation state along exterior binding sites. A very surprising and interesting finding of this study revealed that annealing applied during the SA leads to a decrease in peptide array size with increasing temperature. This is counterintuitive to classical crystallization theory and is explained by a reduced availability of alpha helical peptides for crystal growth at elevated temperatures. Besides this finding, using chemical linkage of oligomeric chains of glycine as well as oligo(ethylene glycol) proved to be another powerful tool to control the size and shape of the peptide nanostructures by solution-based SA. It again verifies the robustness of the SA. Admittedly, further iterations are needed to optimize the design process to take into account the possibility of the realization of various space groups for a single amino acid sequence. Nonetheless, the herein presented approach demonstrates that the computational design of de-novo peptides is a promising way to derive a number of versatile and robust nanomaterials with high precision and functionality. Furthermore, first experiments towards 3D capsid assemblies showed that the synthesis of corresponding amino acid sequences is feasible though challenging due to the high degree of hydrophobicity. The SA of the peptides most likely needs to be fine-tuned to end up in the regime of the phase diagram where capsid formation is preferred. Studies along this direction are under way.
Publications
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Computationally designed peptides for self-assembly of nanostructured lattices. Science Advances 09 Sep 2016:
Vol. 2, no. 9, e1600307
Polzer, F.; Zhang, H.V.; Haider, M. J.; Tian, Y.; Kiick, K. L.; Saven, J. G.; Pochan, D. J.
