Unraveling the Effects of Cationic Peptides on Vesicle Structures: Insights into Peptide-Membrane Interactions.

ABSTRACT

Antimicrobial resistance is a pressing global health issue, with millions of lives at risk by 2050, necessitating the development of alternatives with broad-spectrum activity against pathogenic microbes. Antimicrobial peptides provide a promising solution by combating microbes, modulating immunity, and reducing resistance development through membrane and intracellular targeting. PuroA, a synthetic peptide derived from the tryptophan-rich domain of puroindoline A, exhibits potent antimicrobial activity against various pathogens, while the rationally designed P1 peptide demonstrates enhanced antimicrobial activity with its specific composition. This paper investigates the concentration-dependent effects of these cationic peptides on distinct types of vesicles representing strong-negative bacterial cell membranes (S-vesicles), weak-negative bacterial cell membranes (W-vesicles), and mammalian cell membranes (M-vesicles). To investigate the interactions between the peptides and vesicles, small-angle neutron scattering experiments were conducted. The cationic peptides, PuroA and P1, interact with S-vesicles through electrostatic interactions, leading to distinct effects. PuroA accumulates on the vesicle surface, increasing Rcore and Rtotal, aligning with the carpet model. P1 disrupts the vesicle structure at higher concentrations, consistent with the detergent model. Neither peptide significantly affects W-vesicles, emphasizing the role of charge. In uncharged M-vesicles, both peptides decrease Rcore and Rtotal and increase tshell, indicating peptide insertion and altered bilayer properties. These findings provide valuable insights into peptide-membrane interactions and their impact on vesicle structures. Furthermore, the implications of these findings extend to the potential development of innovative antimicrobial agents and drug delivery systems that specifically target bacterial and mammalian membranes. This research contributes to the advancement of understanding peptide-membrane interactions and lays the foundation for the design of approaches for targeting membranes in various biomedical applications.