Antimicrobial effects of fibrous unit in modular self-assembling peptides

The strategy of using modular self-assembling peptides (MSAPs) forming nanofibers (NFs) in the "recognition-capture" antibacterial process has gained significant attention. In this study, we developed a series of MSAPs and investigated the structural determinants governing their antibacterial efficacy, with a focus on the β-sheet content and nanofiber mechanics. The variation in β-sheet content (Δβ-sheet) of MSAPs after incubation with lipopolysaccharides (LPS) was contingent on the peptide structure of the fibrous subunits. A pronounced negative correlation was observed between Δβ-sheet and the minimum inhibitory concentration (MIC), indicating that enhanced β-sheet content directly potentiated antimicrobial activity. Furthermore, the Young’s modulus of the NFs was quantitatively characterized by AFM, exhibited an inverse relationship with MIC values. This suggests that the higher Young’s modulus of NFs confer superior bacterial inhibition. Meanwhile, we demonstrated that MSAPs at concentrations lower than MIC possess strong anti-infection potential. It was found that the NFs of MSAPs with hydrophilic fibrous units entangled around the bacteria more than hydrophobic ones, showing higher invasion inhibition of bacteria to host cells. This understanding of the antimicrobial activity of MSAPs may help us design more effective antibacterial peptides.