Conformation-Directed Formation of Self-Healing Diblock Copolypeptide Hydrogels via Polyion Complexation

Abstract

Synthetic diblock copolypeptides were designed to incorporate oppositely charged ionic segments that form β-sheet-structured hydrogel assemblies via polyion complexation when mixed in aqueous media. The observed chain conformation directed assembly was found to be required for efficient hydrogel formation and provided distinct and useful properties to these hydrogels, including self-healing after deformation, microporous architecture, and stability against dilution in aqueous media. While many promising self-assembled materials have been prepared using disordered or liquid coacervate polyion complex (PIC) assemblies, the use of ordered chain conformations in PIC assemblies to direct formation of new supramolecular morphologies is unprecedented. The promising attributes and unique features of the β-sheet-structured PIC hydrogels described here highlight the potential of harnessing conformational order derived from PIC assembly to create new supramolecular materials.

Enhancing the Potency of Antimicrobial Peptides through Molecular Engineering and Self-Assembly

“…Different PA molecules have been designed and exploited by numerous research groups, including the labs from Stupp, Tirrell, Deming, Guler, Hamley, and others. [20][21][22][23][24][25][26][27][28][29] As proof of concept, we selected the antimicrobial peptide WMR, which has been previously identified in our lab as a modification of the native sequence of myxinidin, as the key functionality to be displayed in the self-assembled nanomaterials. [30][31][32] Myxinidin is a marine antimicrobial peptide isolated from the epidermal mucus of hagfish (Myxine [33][34] It is one of the shortest AMPs discovered so far (12-amino-acid peptide: NH 2 -GIHDILKYGKPS-CONH 2 ) with potent antibacterial activity against a wide range of bacteria and yeast pathogens.…”

Self-Sorting Microscale Compartmentalized Block Copolypeptide Hydrogels

“…Our lab has created a variety of diblock copolypeptide hydrogels (DCH), [15][16][17][18] where some have been developed for applications including localized delivery of molecules and cells within central nervous system tissues, 19,20 and as antimicrobial coatings for wounds and surgery. 21 DCH are readily formulated by addition of solid copolypeptide to aqueous media that may contain various molecules or cells, resulting in hydrogel formation at moderate temperatures and in different buffers or media.…”

“…21 DCH are readily formulated by addition of solid copolypeptide to aqueous media that may contain various molecules or cells, resulting in hydrogel formation at moderate temperatures and in different buffers or media. [15][16][17][18] These physically associated hydrogels are composed of branched and tangled nanoscale tape-like assemblies that can be deformed by applied stress and injected through narrow diameter needles, after which they rapidly selfheal into elastic gel networks. [15][16][17][18] DCH are also porous hydrogels that contain microscopic water-filled channels that allow for rapid diffusion of molecules within the networks.…”

“…[15][16][17][18] These physically associated hydrogels are composed of branched and tangled nanoscale tape-like assemblies that can be deformed by applied stress and injected through narrow diameter needles, after which they rapidly selfheal into elastic gel networks. [15][16][17][18] DCH are also porous hydrogels that contain microscopic water-filled channels that allow for rapid diffusion of molecules within the networks. [15][16][17][18] Inspired by the multicomponent hydrogel strategies described above, we sought to introduce compartmentalization and mechanical enhancement into DCH through combination of different block copolypeptide components that would generate dual compartment DCH (hereafter DCH DC ).…”

“…[15][16][17][18] DCH are also porous hydrogels that contain microscopic water-filled channels that allow for rapid diffusion of molecules within the networks. [15][16][17][18] Inspired by the multicomponent hydrogel strategies described above, we sought to introduce compartmentalization and mechanical enhancement into DCH through combination of different block copolypeptide components that would generate dual compartment DCH (hereafter DCH DC ). Since DCH networks are formed by direct self-assembly of copolypeptides in water, it was necessary to develop mixtures of DCH that could self-sort into two distinct networks during assembly, as opposed to co-assembling into a single network of mixed composition.…”