3.1 Synthesis, peptide design and hydrogelation of Zn-responsive hydrogels Amphiphilic peptides have been extensively investigated over the years for their role in self-assembly. Therefore, an amphiphilic sequence of amino acids was selected, consisting of one lipophilic (Leu, Ile, Val) and one hydrophilic (Lys, His) end. Two short amphiphilic peptides, Ac-LIVKHH-NH 2 (P1) and Fmoc-LIVKHH-NH 2 (P2), were designed based on their binding affinity to Zn(II) via their two histidine moieties. These histidine moieties can be deprotonated under physiological conditions, yielding imidazoles capable of coordinating to divalent zinc. Each peptide coordinates to two of the four sites available to the typically tetrahedral coordinated Zn(II), leading to a metal-peptide crosslinking node. 24, 50-52 (Fig. ) Furthermore, N-terminus modification on one of the peptides is expected to exert a greater influence on hydrogel formation, particularly due to the presence of the Fmoc group in comparison with its acetylated analogue. The Fmoc group, known for its π-π stacking effects, facilitates the formation of stiffer hydrogels. 18 The minimum gelation concentration was determined through dissolution of P1 and P2 in Milli-Q water at physiological conditions at different peptide concentrations. For P1, this was found to be 2 wt% (20 mg mL -1 ), while P2 displayed a minimum gelation concentration of 0.3 wt% (3 mg mL -1 ). To test if the peptides indeed show stimuli responsiveness to Zn(II) ions, Zn(OAc) 2 was added to a peptide solution and the pH was readjusted to pH ~ 7. While a solution of P2 in Milli-Q water takes about 5 minutes to form a hydrogel, the observed gelation time can be reduced to seconds in the presence of 0.5 equiv. Zn(OAc) 2 , clearly demonstrating the influence of Zn(II) ions on the gelation behavior of P2.