Heterotypic Supramolecular Hydrogels Formed by Noncovalent Interactions in Inflammasomes.

Adrianna N Shy,Bing Xu,Zhaoqianqi Feng,Huaimin Wang

doi:10.3390/molecules26010077

Abstract

The advance of structural biology has revealed numerous noncovalent interactions between peptide sequences in protein structures, but such information is less explored for developing peptide materials. Here we report the formation of heterotypic peptide hydrogels by the two binding motifs revealed by the structures of an inflammasome. Specifically, conjugating a self-assembling motif to the positively or negatively charged peptide sequence from the ASCPYD filaments of inflammasome produces the solutions of the peptides. The addition of the peptides of the oppositely charged and complementary peptides to the corresponding peptide solution produces the heterotypic hydrogels. Rheology measurement shows that ratios of the complementary peptides affect the viscoelasticity of the resulted hydrogel. Circular dichroism indicates that the addition of the complementary peptides results in electrostatic interactions that modulate self-assembly. Transmission electron microscopy reveals that the ratio of the complementary peptides controls the morphology of the heterotypic peptide assemblies. This work illustrates a rational, biomimetic approach that uses the structural information from the protein data base (PDB) for developing heterotypic peptide materials via self-assembly.

Highlights

Peptides, as the building blocks for supramolecular assemblies, have received considerable research attention [1,2,3,4,5,6,7] because peptides are biodegradable and accessible
Drawing inspiration from the protein structures in the work of Wu et al, in which they explored the assembly of ASC dependent inflammasomes AIM2 and NLRP3 [40], we used two peptide sequences from the ASCPYD filaments derived from the inflammasome (PDB ID: 3J63) to enable heterotypic self-assembly
We tested the formation of hydrogels by mixing the oppositely charged peptides

Summary

Introduction

As the building blocks for supramolecular assemblies, have received considerable research attention [1,2,3,4,5,6,7] because peptides are biodegradable and accessible. When the concentration of a self-assembling peptide reaches a certain threshold, intermolecular noncovalent interactions would result in a network of peptide nanofibers, which are able to hold water in the interstitial spaces to form hydrogels [8,9]. The formation of peptide hydrogels usually originates from interactions on three levels: primary (the atomic interactions between molecules), secondary (the interactions between two or more monomeric structures to create ribbons, rods, etc.), and tertiary (the overall structure of the gel determined by individual aggregates) [8] The assembly of these peptides by these three categories of interactions determine the overall characteristics of peptide-based hydrogels. While most of the studies have focused on the hydrogels made of one type of peptide building blocks, that is, homotypic hydrogels, the exploration on heterotypic peptide hydrogels is rather limited [28,29,30,31]

Methods

Results

Conclusion