Tailoring Supramolecular Peptide–Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting

Abstract

Physical hydrogels are extensively used in a wide range of biomedical applications. However, different applications require hydrogels with different mechanical and structural properties.Tailoring these properties demands exquisite control over the supramolecular interactions involved. Here we show that it is possible to control the mechanical properties of hydrogels using de novo designed coiled coil peptides with different affinities for dimerization. Four different non-orthogonal peptides, designed to fold into four different coiled coil heterodimers with dissociation constants spanning from µM to pM, were conjugated to star-shaped 4-armpoly(ethylene glycol) (PEG). The different PEG-coiled coil conjugates self-assemble as a result of peptide heterodimerization. Different combinations of PEG-peptide conjugates assemble into PEG-peptide networks and hydrogels with distinctly different thermal stabilities, supramolecular and rheological properties, reflecting the peptide dimer affinities. We also demonstrate that it is possible to rationally modulate the self-assembly process by means of thermodynamic self-sorting by sequential additions of non-pegylated peptides. The specific interactions involved in peptide dimerization thus provides means for programmable and reversible self-assembly of hydrogels with precise control over rheological properties, which 2 can significantly facilitate optimization of their overall performance and adaption to different processing requirements and applications.

Self-Healing, Self-Assembled β-Sheet Peptide–Poly(γ-glutamic acid) Hybrid Hydrogels

“…These stiffness values are in the region of many soft tissues and compare well to those from previously published peptide–polymer hybrid hydrogel systems. 20−22,31−34 …”

“…One way to approach this engineering problem would be to develop a scaffold that can self-heal, providing a recovery in mechanical properties following an exposure to large strains. In previous work, peptides designed to guide the organization of polymer networks through peptide self-assembly have included coiled-coils 20−22 and β-sheets. 23−25 Specifically the self-assembly of β-sheets motifs have been utilized in block copolymers 26−28 as nanofiber-forming grafts to synthetic polymer networks 29,30 and as cross-links in hydrogels.…”

Influence of Network Topology on the Viscoelastic Properties of Dynamically Crosslinked Hydrogels

“…As the crosslink, we used a synthetic coiled coil (CC; Figure 1). CCs are self-assembled superhelical structures (Lupas, 1996;Woolfson, 2005) have further evolved into tunable protein-based building blocks for synthetic biology and materials science where they find application in protein origami structures (Fletcher et al, 2013;Ljubetič et al, 2017) and as crosslinks for polymeric materials (Petka et al, 1998;Wang et al, 1999;Yang et al, 2006;Shen et al, 2007;Dånmark et al, 2016;Tunn et al, 2018;Tunn et al, 2019). Based on their natural abundance in biological materials and their generally established application as molecular building blocks, we consider CCs to be excellent tunable crosslinks for biomimetic material design.…”

Calcium ion‐induced self‐healing pattern of chemically crosslinked poly(acrylic acid) hydrogels

“…Efforts have been made towards functional hydrogels in order to extend their mechanical strength and self‐repair properties via the addition of fillers or adhesives . The self‐healing hydrogels follow various types of mechanisms, such as hydrogen bonding, ionic interactions, host–guest interactions, crystallization, π – π interactions and multiple intermolecular interactions, which are involved in crack repair and re‐formation of their network structures …”

“…9,10 The self-healing hydrogels follow various types of mechanisms, such as hydrogen bonding, ionic interactions, host-guest interactions, crystallization, -interactions and multiple intermolecular interactions, which are involved in crack repair and re-formation of their network structures. [11][12][13][14][15][16][17][18] Poly(acrylic acid) (PAA) is a hydrophilic and superabsorbent polymer which is frequently used in various applications, especially in drug delivery due to the presence of carboxyl groups which induce hydrophilicity, ionic character and pH responsiveness. Several studies have been reported regarding the use of PAA gels in self-healing applications by exploiting the carboxyl functionality which mediates hydrogen bonding across a damaged hydrogel.…”