Ubiquicidin-Derived Peptides Selectively Interact with the Anionic Phospholipid Membrane.

Ubiquicidin (UBI)/ribosomal protein S30 (RS30) is an intracellular protein with antimicrobial activities against various pathogens. UBI (29-41) and UBI (31-38) are two crucial peptides derived from Ubiquicidin, which have shown potential as infection imaging probes. Here, we report the interactions of UBI-derived peptides with anionic and zwitterionic phospholipid membranes. Our isothermal titration calorimetry results show that both peptides selectively interact with the anionic phospholipid membrane (a model bacterial membrane) and reside mainly on the membrane surface. The interaction of UBI-derived peptides with the anionic phospholipid membrane is exothermic and driven by both enthalpy (ΔH) and entropy (ΔS), with the entropic term TΔS being greater than ΔH. This large entropic term can be a result of the aggregation of the anionic vesicles, which is confirmed by dynamic light scattering (DLS) measurements. DLS data show that vesicle aggregation is enhanced with increasing peptide-to-lipid molar ratios (P/L) and is found to be more pronounced in the case of UBI (29-41). DLS results are found to be consistent with independent transmission measurements. To study the effects of UBI-derived peptides on the microscopic dynamics of the model bacterial membrane, quasielastic neutron scattering (QENS) measurements have been carried out. The QENS results show that both peptides restrict the lateral motion of the lipid within the leaflet. UBI (29-41) acts as a stronger stiffening agent, hindering the lateral diffusion of lipids more efficiently than UBI (31-38). To our knowledge, this is the first report illustrating the mechanism of interaction of UBI-derived peptides with model membranes. This study also has implications for the improvement and design of antimicrobial peptide-based infection imaging probes.