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

## TL;DR

This paper introduces a new method to strengthen hydrogels using self-assembling peptides and controlled polymerization, inspired by natural biopolymers.

## Contribution

A modular strategy combining peptide self-assembly and sequence-controlled polymerization to enhance hydrogel mechanical properties.

## Key findings

- Peptide sequences were tuned to control supramolecular organization and enable efficient topotactic polymerization.
- Hydrogels with DA-PAs showed 200-fold increased stiffness and over 1,000-fold increased viscous dissipation.
- Modifying PEG cross-linker chemistry modulated hydrogel stiffness by nearly an order of magnitude.

## Abstract

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.