Hierarchical Composite Self-Sorted Gel Noodles

Multicomponent systems provide extra control over supramolecular systems and are an easy method for introducing functionality. For example, bioactive peptides can be incorporated into the gel network to improve cell culture viability. Here we discuss multicomponent systems composed of two structurally similar functionalised dipeptides: 2NapLG and 2NapFF. 2NapFF self-assembles into long 1D structures (worm-like micelles) at high pH (pH 10.5) and forms viscous solutions. The small-angle neutron scattering (SANS) data from 2NapFF is best fit to a hollow cylinder model at concentrations of 5 mg/mL and greater. 2NapLG forms spherical micelles in solution at high pH, giving non-viscous solutions. SANS data from 2NapLG are of low intensity and best fit to a power law only. Mixing these two components results in greatly increased viscosity compared to the individual components alone at the same concentrations. We have used a variety of techniques, including circular dichroism, SANS and NMR spectroscopy to investigate how these two components interact during self-assembly at high pH.<br/><br/>According to SANS data, the multicomponent systems form hollow cylinders with different radii and thickness to those formed by 2NapFF alone. We have used numerous NMR experiments to further investigate the interactions between 2NapLG and 2NapFF in solution at high pH. The integrals corresponding to protons on 2NapFF measured during ¹H NMR spectroscopy show decreased intensity in the presence of 2NapLG, suggesting that more 2NapFF molecules are in the assembled state in the multicomponent system. We were able to confirm that 2NapLG forms physical interactions with the structures formed by 2NapFF using nuclear Overhauser effect (NOE) NMR experiments. In samples of 2NapLG alone, we observed a positive NOE difference. This confirms that 2NapLG behaves like a small molecule in solution at high pH, i.e does not form persistent structures. However, in the presence of 2NapFF, a negative NOE difference was observed. This shows that 2NapLG does interact with the large structures formed by 2NapFF. What is perhaps most interesting is that a negative NOE difference was also detected on the aromatic protons. This was completely unexpected as the methyl and aromatic protons are very far apart on the molecule. This implies exchange with the micelles that is not observed in 2NapLG alone and within these structures, the methyl group is close enough in space to interact with the aromatic protons. For 2NapFF, the aromatic signal (most likely from the aromatic rings on the phenylalanine residues was selectively inverted. We observed NOE to other aromatic protons and to the CH₂ groups. The NOE difference is negative, as we would expect from the formation of worm-like micelles. No NOE was observed to protons on 2NapLG. This implies that the assembly between 2NapFF and 2NapLG is orthogonal, i.e. the two molecules are not intimately mixed within the structures.<br/><br/>2NapFF can be used to form supramolecular noodles. We expected that the 2NapFF/2NapLG multicomponent system would form mechanically superior noodles to 2NapFF alone according to data from viscosity and small-angle scattering experiments. This hypothesis was confirmed using nanoindentation. While 2NapFF forms supramolecular hydrogels on a reduction in pH, 2NapLG forms crystals under the same conditions. By exploiting this behaviour, we have formed crystals within supramolecular noodles the first reporting, to our knowledge, of such behaviour.