Programming Hydrogel Mechanics via Sequence-Controlled Polymerization Using Peptide Self-Assembly

Hydrogels often have poor mechanical properties due to their high water content and low polymer concentration, which limits their utility in applications that require them to withstand applied forces. Inspired by natural biopolymers such as collagen and actin, which form highly extended fibrillar networks that stiffen biological tissues, we developed a modular strategy that utilizes self-assembling peptides to direct the formation of covalently polymerized diacetylene networks in hydrogels. By systematically tuning peptide sequences, we precisely controlled the supramolecular organization and molecular orientation within the self-assembled nanofibers. This optimization enabled efficient topotactic polymerization of diacetylene moieties within the self-assembling peptides. Peptide sequences that readily promoted polymerization formed hydrogels with superior viscoelastic properties. Incorporation of these diacetylene peptide amphiphiles (DA-PAs) into covalently cross-linked poly(ethylene glycol) (PEG) hydrogels increased their mechanical stiffness 200-fold, while increasing viscous dissipation over 1,000 times. Modifying the chemical structure of the PEG cross-linker tuned the interfacial interactions between the covalent PEG and DA-PA networks, modulating stiffness by almost an order of magnitude. Since the DA-PAs readily dissolve in water prior to polymerization, they can be incorporated into most hydrogel systems. Adding them to alginate hydrogels led to an almost 20-fold increase in the hydrogel stiffness. This approach, merging peptide-driven supramolecular chemistry with precise covalent polymerization, provides powerful and versatile pathways for fabricating mechanically robust materials that offer new insights into how hierarchical structures can be used to improve hydrogel mechanics.