Notably, the effect of ECC on the binding affinities of etidocaine and TPP is opposite to its effect on the calcium-binding affinity which decreased upon applying ECC. This can be explained by the different binding mechanisms of calcium and small molecules, such as etidocaine and TPP. The main driving forces for calcium binding to a membrane with PC lipids are the direct electrostatic interactions with phosphate oxygens, as also seen in the table where the majority of calcium-lipid interactions occur with phosphate oxygens.