Metal-Biosurfactant Complexes Characterization: Binding, Self-Assembly and Interaction with Bovine Serum Albumin.

Studies on the specific and nonspecific interactions of biosurfactants with proteins are broadly relevant given the potential applications of biosurfactant/protein systems in pharmaceutics and cosmetics. The aim of this study was to evaluate the interactions of divalent counterions with the biomolecular anionic biosurfactant surfactin-C15 through molecular modeling, surface tension and dynamic light scattering (DLS), with a specific focus on its effects on biotherapeutic formulations. The conformational analysis based on a semi-empirical approach revealed that Cu2+ ions can be coordinated by three amide nitrogens belonging to the surfactin-C15 cycle and one oxygen atom of the aspartic acid from the side chain of the lipopeptide. Backbone oxygen atoms mainly involve Zn2+, Ca2+ and Mg2+. Subsequently, the interactions between metal-coordinated lipopeptide complexes and bovine serum albumin (BSA) were extensively investigated by fluorescence spectroscopy and molecular docking analysis. Fluorescence results showed that metal-lipopeptide complexes interact with BSA through a static quenching mechanism. Molecular docking results indicate that the metal-lipopeptide complexes are stabilized by hydrogen bonding and van der Waals forces. The biosurfactant-protein interaction properties herein described are of significance for metal-based drug discovery hypothesizing that the association of divalent metal ions with surfactin allows its interaction with bacteria, fungi and cancer cell membranes with effects that are similar to those of the cationic peptide antibiotics.

Counterion-mediated pattern formation in membranes containing anionic lipids.

Most lipid components of cell membranes are either neutral, like cholesterol, or zwitterionic, like phosphatidylcholine and sphingomyelin. Very few lipids, such as sphingosine, are cationic at physiological pH. These generally interact only transiently with the lipid bilayer, and their synthetic analogs are often designed to destabilize the membrane for drug or DNA delivery. However, anionic lipids are common in both eukaryotic and prokaryotic cell membranes. The net charge per anionic phospholipid ranges from -1 for the most abundant anionic lipids such as phosphatidylserine, to near -7 for phosphatidylinositol 3,4,5 trisphosphate, although the effective charge depends on many environmental factors. Anionic phospholipids and other negatively charged lipids such as lipopolysaccharides are not randomly distributed in the lipid bilayer, but are highly restricted to specific leaflets of the bilayer and to regions near transmembrane proteins or other organized structures within the plane of the membrane. This review highlights some recent evidence that counterions, in the form of monovalent or divalent metal ions, polyamines, or cationic protein domains, have a large influence on the lateral distribution of anionic lipids within the membrane, and that lateral demixing of anionic lipids has effects on membrane curvature and protein function that are important for biological control.