Pediocin PA-1-membrane interaction: Unveiling a unique mechanism for targeted eukaryotic membranes

Understanding the molecular intricacies of Pediocin PA-1 interactions with biological membranes reveals a distinctive mechanism with promising implications beyond its effects on prokaryotic membranes. To elucidate the behavior of this bacteriocin, molecular dynamics simulations were performed under both NVT and NPT ensembles, as well as with NγT to accelerate biological processes by applying different surface tensions. The alpha-helix region plays a pivotal role, maintaining a stable orientation perpendicular to the membrane, optimizing interactions and minimizing hydrogen bond resistance. The subsequent poration mechanism, essential for the bacteriocin's cytotoxic potential, involves lipid displacement facilitated by the insertion of the alpha-helix. Notably, the restricted movement of the C-terminal region, stabilized by a disulfide bridge, ensures precise spatial arrangements, enhancing the peptide's effective insertion and poration. Molecular dynamics simulations highlight Pediocin PA-1's impact on membrane properties, including thickness, lipid area, and lateral diffusion. The bacteriocin's hydrophobicity and the selective orientation of its N-terminal region contribute significantly to membrane destabilization, providing key insights into its molecular behavior. Beyond its structural characteristics, Pediocin PA-1 exhibits notable cytotoxic potential against colon cancer cells. Its membrane-disruptive effects, coupled with selective activity towards cancerous cells, position the bacteriocin as a promising candidate for targeted cancer therapy. This study explores the interplay between temperature and surface tension, further advancing our understanding of Pediocin PA-1's versatile behavior. As research progresses, the complex interaction between this bacteriocin and biological membranes not only deepens our understanding of its mechanism but also opens new avenues for potential therapeutic applications.