Tunable Pentapeptide Self‐Assembled β‐Sheet Hydrogels

Abstract

Oligopeptide‐based supramolecular hydrogels hold promise in a range of applications. The gelation of these systems is hard to control, with minor alterations in the peptide sequence significantly influencing the self‐assembly process. We explored three pentapeptide sequences with different charge distributions and discovered that they formed robust, pH‐responsive hydrogels. By altering the concentration and charge distribution of the peptide sequence, the stiffness of the hydrogels could be tuned across two orders of magnitude (2–200 kPa). Also, through reassembly of the β‐sheet interactions the hydrogels could self‐heal and they demonstrated shear‐thin behavior. Using spectroscopic and cryo‐imaging techniques, we investigated the relationship between peptide sequence and molecular structure, and how these influence the mechanical properties of the hydrogel. These pentapeptide hydrogels with tunable morphology and mechanical properties have promise in tissue engineering, injectable delivery vectors, and 3D printing applications.

Stoichiometry-controlled secondary structure transition of amyloid-derived supramolecular dipeptide co-assemblies

“…2d). A difference in peak intensity at 240 and 308 nm was also observed for the FmocFF/ BPY (2:1) gel, since peptide nanofibrous hydrogels are supramolecular aggregates, and in some cases, they have different transparency, which is likely to result in some fraction of the light being scattered, thereby influencing peak intensity 58,59 . High resolution TEM images of the FmocFF and FmocFF/ BPY (1:1) gels showed ribbon-like fibrils, 11-65 and 21-70 nm in width, respectively (Fig.…”

“…Our group also reported a self-assembling single heptad repeat module to form a helical conformation, where the peptide exhibited two negative maxima at around 205 and 218 nm 56 . Previous studies have also explored the relationship between CD and the degree of twisting of β-sheets, showing that strongly twisted β-sheets generate a stronger red shift at the minimum and maximum wavelengths, but do not change the original nature of CD pattern, with one minimum negative band and one maximum positive band [57][58][59] . Thus, the two blue-shifted negative maxima at 203 and 213 nm, along with the positive maximum at 192 nm, observed for FmocFF/BPY (2:1) should be ascribed to the helical conformation, rather than to a twisted β-sheet conformation.…”

“…4), indicating more twisted β-sheet arrangements. Remaining BPY may form π-π interactions with fluorenyl or pyridine rings of dimer of 1:1 FmocFF/BPY and further increase the hydrogenbonding distance between two dimers, weakening the intermolecular forces and hydrogen bonds on the periphery of the β-sheet 58,59 .…”

Supramolecular Hydrogels for Protein Delivery in Tissue Engineering

“…In addition, the initial burst release of protein from this two-layer hydrogel was decreased compared to the single peptide formed hydrogel, which resulted from the higher nanofiber density provided by the additional layer [ 40 ]. The morphology of a self-assembled β-sheet pentapeptide hydrogels could be tuned by altering the charge distribution of the peptide sequence [ 41 ]. The pentapeptide contains three aliphatic isoleucine (I) residues, with potential to form β-sheets, and two aspartic acid (D) residues to improve solubility (DIIID-NH 2 , DDIII-NH 2 and IDIDI-NH 2 ).…”

High-Throughput Peptide Derivatization toward Supramolecular Diversification in Microtiter Plates

“…Moreover, it is acknowledged that subtle chirality/sequence/structure modifications can cause changes in the peptide conformation, association energy landscape, and binding affinity. 18 − 28 In this context, rapidly screening or predicting the behavior of peptide arrays in an efficient manner is also essential for expanding peptide diversity and accelerating their applications as innovative soft materials. 29 At the molecular level, phage display employs the genetic amplification of bacteriophage coat proteins to build libraries for identifying specific recognition sequences.…”