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.