Polymorphic self-organization of Lauroyl peptide in response to pH and concentration

Amphipathic peptides are attractive building blocks for the preparation of self-assembling, bio-inspired, and stimuli responsive nanomaterials with pharmaceutical interest. The bioavailability of these materials can be improved with the insertion of d amino acid residues to avoid fast proteolysis in vivo. With this knowledge, a new lauroyl peptide consisting of a sequence of glycine, glycine, d-serine, and d-lysine was designed. In spite of its simple sequence, this lipopeptide self-assembles into spherical micelles at acid pH, when the peptide moiety adopts disordered conformations. Self-aggregates reshape toward fibers at basic pH, following the conformational transition of the peptide region from random coil to β-sheet. Finally, hydrogels are achieved at basic pH and higher concentrations. The transition from random coil to β-sheet conformation of the peptide headgroup obtained by increasing pH was monitored by circular dichroism and vibrational spectroscopy. A structural analysis, performed by combining dynamic light scattering, small-angle X-ray scattering, transmission electron microscopy, and molecular dynamic simulations, demonstrated that the transition allows the self-assemblies to remodel from spherical micelles to rodlike shapes, to long fibers with rectangular cross-section and a head-tail-tail-head structure. The viscoelastic behavior of the hydrogels formed at the highest pH was investigated by rheology measurements.