Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH 2 , FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillinresistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drugrelated side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the manage ment of microbeinfected diabetic wounds.

Developing novel immobilization methods to maximize the catalytic performance of enzymes has been a permanent pursuit of scientific researchers. Engineered Escherichia coli biofilms have attracted great concern as surface display platforms for enzyme immobilization. However, current biological conjugation methods, such as the SpyTag/SpyCatcher tagging pair, that immobilize enzymes onto E. coli biofilms seriously hamper enzymatic performance. Through phage display screening of lipase-binding peptides (LBPs) and co-expression of CsgB (nucleation protein of curli nanofibers) and LBP2-modified CsgA (CsgALBP2, major structural subunit of curli nanofibers) proteins, we developed E. coli BL21::ΔCsgA-CsgB-CsgALBP2 (LBP2-functionalized) biofilms as surface display platforms to maximize the catalytic performance of lipase (Lip181). After immobilization onto LBP2-functionalized biofilm materials, Lip181 showed increased thermostability, pH, and storage stability. Surprisingly, the relative activity of immobilized Lip181 increased from 8.43 to 11.33 U/mg through this immobilization strategy. Furthermore, the highest loading of lipase on LBP2-functionalized biofilm materials reached up to 27.90 mg/g of wet biofilm materials, equivalent to 210.49 mg/g of dry biofilm materials, revealing their potential as a surface with high enzyme loading capacity. Additionally, immobilized Lip181 was used to hydrolyze phthalic acid esters, and the hydrolysis rate against dibutyl phthalate was up to 100%. Thus, LBP2-mediated immobilization of lipases was demonstrated to be far more advantageous than the traditional SpyTag/SpyCatcher strategy in maximizing enzymatic performance, thereby providing a better alternative for enzyme immobilization onto E. coli biofilms.

A monomer-targeting strategy based on solution-phase biopanning to obtain peptide inhibitors increases the suppression efficiency and reduces the cytotoxicity of amylin.

Phenol-soluble modulin α3 (PSMα3) can self-assemble into fibrous assemblies with a unique "cross-α" sheet structure, which serves as a key virulence factor in the infection of Staphylococcus aureus. However, the structure−cytotoxicity relationships of PSMα3 still remain elusive. Herein, we utilized the strategy of salt-inducing assembly polymorphism to controllably prepare three PSMα3 assemblies with morphological and structural distinctions, including amorphous aggregates (AAs), rigid fibrils (RFs), and oligomers/curvilinear fibrils (OCFs), which provided a convincing method to facilitate the structure−cytotoxicity investigation of PSMα3 assemblies. Our results affirmed that amyloid fibrillation was essential for the enhancement of PSMα3 cytotoxicity, which was proved based on the evidence that RFs and OCFs both triggered more obvious cytotoxicity than AAs. Furthermore, our study also demonstrated that the cytotoxicity was severely dependent on the size and structure of PSMα3 fibrils. In detail, smaller OCFs rich in α-helices exhibited stronger virulence than RFs with larger sizes and low α-helical contents. The cytotoxicity caused by such fibrils was achieved via a membrane-disrupting mechanism, in which RFs and OCFs might be prone to membrane thinning and perforation, respectively. This strategy of salt-inducing PSMα3 assembly polymorphism facilitated the comprehension of the relationship between the characteristics of PSMα3 assemblies and their cytotoxicity and was also helpful to understanding the intrinsic assembly mechanism of the PSMα3.

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