Multivalent Interactions Enable the Natural Alkaline Amino Acids to Transmute into Macroscopic Adhesive Materials.

Natural alkaline amino acids (aAAs) have been found to interact with tannic acid (TA) in aqueous solution via multiple noncovalent interactions, giving rise to the formation of water-immiscible supramolecular copolymers (aAAs/TA). The driving forces and the internal structures of the supramolecular copolymers were characterized by nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), ζ-potential, elemental analysis (EA), and scanning electron microscopy (SEM). Rheological and lap shear adhesion measurements identify that the aAAs/TA soft materials exhibit wet and underwater adhesion, shear thinning, and self-healing behavior. This supramolecular adhesive can be utilized as both injectable materials and self-gelling powder. Another feature of the aAAs/TA adhesives is the acceptable cellular compatibility with L-929 cells, which enables the supramolecular copolymers to be potential soft materials for health care and bio-related applications. The work highlights that the cross-linked supramolecular polymerization strategy enables minimalistic biomolecules to emulate the functions of complicated proteins secreted by aquatic organisms.

Modular co-assembly of peptides and polyoxometalates into underwater adhesives with photoluminescence and adjustable adhesion.

Supramolecular polymerization between cationic peptides and anionic polyoxometalates has emerged as a promising strategy for the creation of peptide-based biomimetic underwater adhesives. However, the extremely rigorous requirements for peptide design are an important obstacle to the fabrication of available peptide adhesives with controlled adhesion and versatile functionality. Inspired by marine sessile organisms in nature, here we reported a modular co-assembly method to easily produce peptide/polyoxometalate underwater adhesive materials through mixing two complementary cationic peptides (Pep1 and Pep2) with a single anionic polyoxometalate K6H[SiW9V3O40] in aqueous solution, which are not possible to be obtained from an individual peptide module. We demonstrated that the relatively hydrophobic Pep1 contributes to the bulk cohesion of the resulting adhesive, while the relatively hydrophilic Pep2 not only enables the interfacial adhesion but also regulates the bulk cohesion of the Pep1/Pep2/SiW9V3 adhesive. Rheological and shear adhesion tests showed that the macroscopic adhesion performance of the resulting adhesive materials could be conveniently adjusted by simply changing the molar ratio of the complementary peptide modules without any complicated peptide design. Interestingly, the luminescence properties of K11[Eu(PW11O39)2] (labelled as EuPW11) could be maintained within the Pep1/Pep2/EuPW11 adhesive even in a water environment. The lifetime of the Pep1/Pep2/EuPW11 adhesive was 2.19 ms. The fluorescence quantum yield of the Pep1/Pep2/EuPW11 adhesive was measured to be 27.46%. This study unveils that the modular co-assembly method can effectively simplify the material design of peptide/polyoxometalate underwater adhesives, which will significantly broaden the horizon of material pools and extend their availability space.

Nano-Antimicrobial Peptides Based on Constitutional Isomerism-Dictated Self-Assembly.

Self-assembly has been identified as an innovative strategy for improving the antimicrobial efficacy and bioavailability of short peptides. However, the detailed molecular information of short peptides linking to the self-assembly structures and antimicrobial activity remains to be more clearly understood. This work reported that the constitutional isomeric sequences of cationic peptides showed a significant impact on their antimicrobial activity. We investigated the self-assembly structures of two constitutional isomeric peptides Ac-RFSFSFR-NH2 and Ac-SFRFRFS-NH2, which contained the same serine, alkaline, and phenylalanine residues but in a different order. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that the constitutional isomers self-assembled into different morphologies in an aqueous solution. The sequence with alkaline residues located at both termini of the peptide favored the formation of ß-sheet conformation and nanofibers, while irregular nanospheres were observed when positioning the alkaline residues at the center of the isomeric peptide. The ζ-potential measurements showed that the Ac-RFSFSFR-NH2 nanofibers had a net potential of +17.4 mV, whereas the apparent potential of Ac-SFRFRFS-NH2 nanospheres dropped steeply to +1.0 mV. These differences of the constitutional isomeric peptides were directly reflected in their antimicrobial activities. In comparison with the peptide Ac-SFRFRFS-NH2, the constitutional isomer Ac-RFSFSFR-NH2 exhibited much higher antimicrobial efficacy against Gram-positive Staphylococcus aureus and Bacillus subtilis and Gram-negative Escherichia coli and Pseudomonas aeruginosa. Moreover, several pairs of constitutional isomeric peptides with a similar sequence layout yielded the same outcome. These collective results not only highlight the importance of the isomeric sequence on the antimicrobial efficacy of short peptides but also increase further potential in optimizing the design of self-assembled nano-antimicrobial peptides (AMPs).

Exploiting Redox-Complementary Peptide/Polyoxometalate Coacervates for Spontaneously Curing into Antimicrobial Adhesives.

Recently, there has been a wave of reports on the fabrication of peptide-based underwater adhesives with the aim of understanding the adhesion mechanism of marine sessile organisms or creating new biomaterials beyond nature. However, the poor shear adhesion performance of the current peptide adhesives has largely hindered their applications. Herein, we proposed to sequentially perform the interfacial adhesion and bulk cohesion of peptide-based underwater adhesives using two redox-complementary peptide/polyoxometalate (POM) coacervates. The oxidative coacervates were prepared by mixing oxidative H5PMo10V2O40 and cationic peptides in an aqueous solution. The reductive coacervates consisted of K5BW12O40 and cysteine-containing reductive peptides. Each of the individual coacervate has well-defined spreading capacity to achieve fast interfacial attachment and adhesion, but their cohesion is poor. However, after mixing the two redox-complementary coacervates at the target surface, effective adhesion and spontaneous curing were observed. We identified that the spontaneous curing resulted from the H5PMo10V2O40-regulated oxidization of cysteine-containing peptides. The formed intermolecular disulfide bonds improved the cross-linking density of the dual-peptide/POM coacervates, giving rise to the enhanced bulk cohesion and mechanical strength. More importantly, the resultant adhesives showcased excellent bioactivity to selectively suppress the growth of Gram-positive bacteria due to the presence of the polyoxometalates. This work raises further potential in the creation of biomimetic adhesives through the orchestrating of covalent and noncovalent interactions in a sequential fashion.

Protein-Based Nano-Vessels Facilitates the Victoria Blue B Mediated Inhibition of Amyloid Fibrillation.

Amyloid fibrils are associated with a number of serious and incurable diseases. The understanding of the pathogenic formation of amyloid proteins is progressing. Nonetheless, no treatment is available to deal with amyloid diseases. It is reported here that victoria blue B (VBB) contains an intrinsic marginal inhibitory activity toward protein fibrillation. Moreover, when VBB is co-assembled with scaffold proteins to form fluorescent protein nano-vessels (VBB-FPNs), these complexes show much improved fibrillation inhibitory effects. VBB-FPNs can effectively inhibit lysozyme fibrils formation likely through delaying the nucleation and elongation in a concentration-dependent manner as shown by fluorescent assay, circular dichroism, transmission electron microscopy, and atomic force microscopy. This work describes a new inhibitor of protein fibrillation and provides a new means to enhance the inhibition efficiency of given inhibitors, thus affording a fresh angle to modulate protein fibrillation.

Peptide/glycyrrhizic acid supramolecular polymer: An emerging medical adhesive for dural sealing and repairing.

Medical adhesives have emerged as potential materials for sealing, hemostasis and wound repairing in modern clinical surgery. However, most of existing medical adhesives are still far away from the clinical requirements for simultaneously meeting desirable tissue adhesion, safety, biodegradability, anti-swelling property, and convenient operability. Here, we present an entirely new kind of peptide-based underwater adhesives, which are constructed via cross-linked supramolecular copolymerization between cationic short peptides and glycyrrhizic acid (GA) in an aqueous solution. We revealed the unique molecular mechanism of the peptide/GA supramolecular polymers and underlined the importance of arginine residues in the enhancement of the bulk cohesion of the peptide/GA adhesive. We thus concluded a design guideline that the peptide sequence has to be encoded with multiple arginine termini and hydrophobic residues. The resulting adhesives exhibited effective tissue adhesion, robust cohesion, low cell cytotoxicity, acceptable hemocompatibility, inappreciable inflammation response, appropriate biodegradability, and excellent anti-swelling property. More attractively, the dried peptide/GA powder was able to rapidly self-gel into adhesives by absorbing water, suggesting conveniently clinical operability. Animal experiments showed that the peptide/GA supramolecular polymers could be utilized as reliable medical adhesives for dural sealing and repairing.

Plant Protein-Peptide Supramolecular Polymers with Reliable Tissue Adhesion for Surgical Sealing.

The fusion of protein science and peptide science opens up new frontiers in creating innovative biomaterials. Herein, a new kind of adhesive soft materials based on a natural occurring plant protein and short peptides via a simple co-assembly route are explored. The hydrophobic zein is supercharged by sodium dodecyl sulfate to form a stable protein colloid, which is intended to interact with charge-complementary short peptides via multivalent ionic and hydrogen bonds, forming adhesive materials at macroscopic level. The adhesion performance of the resulting soft materials can be fine-manipulated by customizing the peptide sequences. The adhesive materials can resist over 78 cmH2 O of bursting pressure, which is high enough to meet the sealing requirements of dural defect. Dural sealing and repairing capability of the protein-peptide biomaterials are further identified in rat and rabbit models. In vitro and in vivo assays demonstrate that the protein-peptide adhesive shows excellent anti-swelling property, low cell cytotoxicity, hemocompatibility, and inflammation response. In particular, the protein-peptide supramolecular biomaterials can in vivo dissociate and degrade within two weeks, which can well match with the time-window of the dural repairing. This work underscores the versatility and availability of the supramolecular toolbox in the easy-to-implement fabrication of protein-peptide biomaterials.