Self-assembly of short peptide amphiphiles: the cooperative effect of hydrophobic interaction and hydrogen bonding.

The interplay between hydrogen bonding, hydrophobic interaction and the molecular geometry of amino acid side-chains is crucial to the development of nanostructures of short peptide amphiphiles. An important step towards developing their practical use is to understand how different amino acid side-chains tune hydrophobic interaction and hydrogen bonding and how this process leads to the control of the size and shape of the nanostructures. In this study, we have designed and synthesized three sets of short amphiphilic peptides (I(3)K, LI(2)K and L(3)K; L(3)K, L(4)K and L(5)K; I(3)K, I(4)K and I(5)K) and investigated how I and L affected their self-assembly in aqueous solution. The results have demonstrated a strong tendency of I groups to promote the growth of β-sheet hydrogen bonding and the subsequent formation of nanofibrillar shapes. All I(m)K (m = 3-5) peptides assembled into nanofibers with consistent β-sheet conformation, whereas the nanofiber diameters decreased as m increased due to geometrical constraint in peptide chain packing. In contrast, L groups had a weak tendency to promote β-sheet structuring and their hydrophobicity became dominant and resulted in globular micelles in L(3)K assembly. However, increase in the number of hydrophobic sequences to L(5)K induced β-sheet conformation due to the cooperative hydrophobic effect and the consequent formation of long nanofibers. The assembly of L(4)K was, therefore, intermediate between L(3)K and L(5)K, similar to the case of LI(2)K within the set of L(3)K, LI(2)K and I(3)K, with a steady transition from the dominance of hydrophobic interaction to hydrogen bonding. Thus, changes in hydrophobic length and swapping of L and I can alter the size and shape of the self-assembled nanostructures from these simple peptide amphiphiles.