Zn(II)-Responsive Peptide Hydrogels with Tunable Mechanical Properties

Metal-coordinated peptide assemblies represent a versatile platform for functional biomaterials; here we describe Zn-(II)-driven hydrogelation of short amphiphilic peptides. To this end, we synthesized two short amphiphilic hexapeptides, Ac-LIVKHH-NH₂ and Fmoc-LIVKHH-NH₂, using standard Fmoc/Boc solid-phase peptide synthesis. Upon interaction with Zn-(II) salts in aqueous solution (pH 7), these peptides encapsulate large volumes of water to form metallo-hydrogels. The Zn-(II)-mediated gelation and structural organization of the resulting supramolecular architectures were examined using circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and scanning electron microscopy (SEM), respectively. Oscillatory rheology and thixotropy measurements confirmed the viscoelastic and shear-recoverable properties of the hydrogels. Zn-(II) coordination was found to play a key role in enhancing mechanical robustness, while the thixotropic behavior highlights their potential as injectable carriers and bioinks for 3D printing. Antibacterial assays against Escherichia coli and Staphylococcus aureus further revealed moderate inhibition zones, indicating additional functional utility. Overall, this work provides new insights into the Zn-(II)-responsive assembly of short amphiphilic peptides and establishes a foundation for their development in biomaterials and materials science.