Molecular Scale Insights into Activity of Polyoxometalate as Membrane-Targeting Nanomedicine from Single-Molecule Observations

Abstract

Polyoxometalate (POM) is rapidly emerging as an attractive antimicrobial inorganic cluster that exhibits its antimicrobial activity by attacking the cell membrane. Precise understanding and control of the antimicrobial activity of POM can allow us to design novel functional nanomedicines with high stability, high selectivity, and low cost. Therefore, in this study, we investigated the interaction between POM and a model cell membrane through single-molecule observation and found that the presence of POM causes macroscopic morphological changes in the microbial membrane, and these changes were detectable as modulations in the diffusivity of the membrane. Numerical analyses based on mean square displacement and diffusion length histogram revealed the reduction in the fluidity of the membrane in the presence of POM. Further analysis from single-molecule tracking revealed the formation of pores in the membrane, along with the formation of POM–lipid assemblies. The pores were found to act as diffusion barriers and diffusion trap sites and thus contributed to the reduction in the fluidity of the membrane. Furthermore, pore formation also led to the loss of important functions of the cell membrane. Based on this ability of POM to induce pore formation and form assemblies with membrane lipids, we believe that POM is a promising candidate for use as a membrane-targeting bioactive nanomedicine.