Effect of Divalent Cations on DMPC/DHPC Bicelle Formation and Alignment

Many important classes of biomolecules require divalent cations for optimal activity, making these ions essential for biologically relevant structural studies. Bicelle mixtures composed of short-chain and long-chain lipids are often used in solution- and solid-state NMR structure determination; however, the phase diagrams of these useful orienting media and membrane mimetics are sensitive to other solution components. Therefore, we have investigated the effect of varying concentrations of four divalent cations, Ca²⁺, Mg²⁺, Zn²⁺, and Cd²⁺, on cholesterol sulfate-stabilized DMPC/DHPC bicelles. We found that low concentrations of all the divalent ions are tolerated with minimal perturbation. At higher concentrations Zn²⁺ and Cd²⁺ disrupt the magnetically aligned phase while Ca²⁺ and Mg²⁺ produce more strongly oriented phases. This result indicates that divalent cations are not only required to maintain the biological activity of proteins and nucleic acids; they may also be used to manipulate the behavior of the magnetically aligned phase.