Assembly Properties of an Alanine-Rich, Lysine-Containing Peptide and the Formation of Peptide/Polymer Hybrid Hydrogels.

We are interested in developing peptide/polymer hybrid hydrogels that are chemically diverse and structurally complex. Towards this end, an alanine-based peptide doped with charged lysines with a sequence of (AKA(3)KA)(2) (AK2) was selected from the crosslinking regions of the natural elastin. Pluronic(®) F127, known to self-assemble into defined micellar structures, was employed as the synthetic building blocks. Fundamental investigations on the environmental effects on the secondary structure and assembly properties of AK2 peptide were carried out with or without the F-127 micelles. At a relatively low peptide concentration (~0.5 mg/mL), the F127 micelles are capable of not only increasing the peptide helicity but also stabilizing it against thermal denaturation. At a higher peptide concentration in basic media, the AK2 peptide developed a substantial amount of β-sheet structure that is conducive to the formation of nanofibrils. The fibril formation was confirmed collectively by atomic force microscopy (AFM), small angle neutron scattering (SANS) and transmission electron microscopy (TEM). The assembly kinetics is strongly dependent on solution temperature and pH; an increased temperature and a more basic environment led to faster fibril assembly. The self-assembled nanoscale structures were covalently interlocked via the Michael-type addition reaction between vinyl sulfone-decorated F127 micelles and the lysine amines exposed at the surface of the nanofibers. The crosslinked hybrid hydrogels were viscoelastic, exhibiting an elastic modulus of approximately 17 kPa and a loss tangent of 0.2.