Home Products Cited in Publications Worldwide Programming Hydrogel Mechanics via Sequence-Controlled Polymerization using Peptide Self-assembly
Moghaddam, Abolfazl; Zaman, Maahi; Liou, Sz-Chian; Pashuck, E Thomas
DOI:10.26434/chemrxiv-2025-hs674
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 utilizing 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 self-assembled nanofibers. This optimization enabled efficient topotactic polymerization of diacetylene moieties within the selfassembling peptides. Peptide sequences that readily promoted polymerization formed hydrogels with superior viscoelastic properties. Incorporation of these diacetylene peptide amphiphiles (DA-PAs) into covalently crosslinked 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 crosslinker 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 dissolved 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 hydrogel stiffness. This approach, merging peptide-driven supramolecular chemistry with precise covalent polymerization, provides powerful and versatile pathways for fabricating mechanically robust, biomimetic hydrogels that can be applied to a range of biomedical applications.