Ethylenediaminetetraacetic acid (EDTA) is frequently used in lipid experiments to remove redundant ions, such as Ca2+, from the sample solution. In this work, combining molecular dynamics (MD) simulations and Langmuir monolayer experiments, we show that on top of the expected Ca2+ depletion, EDTA anions themselves bind to phosphatidylcholine (PC) monolayers. This binding, originating from EDTA interaction with choline groups of PC lipids, leads to the adsorption of EDTA anions at the monolayer surface and concentration-dependent changes in surface pressure as measured by monolayer experiments and explained by MD simulations. This surprising observation emphasizes that lipid experiments carried out using EDTA-containing solutions, especially of high concentrations, must be interpreted very carefully due to potential interfering interactions of EDTA with lipids and other biomolecules involved in the experiment, e.g., cationic peptides, that may alter membrane-binding affinities of studied compounds.

Central European Institute of Technology Masaryk University Kamenice 5 625 00 Brno Czech Republic

Department of Mathematics Informatics and Cybernetics University of Chemistry and Technology Technická 5 16628 Prague Czech Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo Náměstí 542 2 16000 Prague Czech Republic

J Heyrovský Institute of Physical Chemistry Czech Academy of Sciences Dolejškova 3 18223 Prague Czech Republic

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