Stealthy Player in Lipid Experiments? EDTA Binding to Phosphatidylcholine Membranes Probed by Simulations and Monolayer Experiments

Ethylenediaminetetraacetic acid (EDTA) is frequentlyused in lipidexperiments to remove redundant ions, such as Ca2+, fromthe sample solution. In this work, combining molecular dynamics (MD)simulations and Langmuir monolayer experiments, we show that on topof the expected Ca2+ depletion, EDTA anions themselvesbind to phosphatidylcholine (PC) monolayers. This binding, originatingfrom EDTA interaction with choline groups of PC lipids, leads to theadsorption of EDTA anions at the monolayer surface and concentration-dependentchanges in surface pressure as measured by monolayer experiments andexplained by MD simulations. This surprising observation emphasizesthat lipid experiments carried out using EDTA-containing solutions,especially of high concentrations, must be interpreted very carefullydue to potential interfering interactions of EDTA with lipids andother biomolecules involved in the experiment, e.g., cationic peptides,that may alter membrane-binding affinities of studied compounds.