Interactions of monovalent salts with cationic lipid bilayers Sarka Pokorna, a Piotr Jurkiewicz, * a Lukasz Cwiklik, ab Mario Vazdar bc and Martin Hof a Received 3rd May 2012, Accepted 21st May 2012 DOI: 10.1039/c2fd20098h The influence of monovalent salts (NaF, NaCl, NaBr, NaClO 4 , KCl) on the properties of lipid bilayers composed of binary mixtures of zwitterionic DOPC (dioleoylphosphatidylcholine) and cationic DOTAP (dioleoyltrimethylammoniumpropane) is experimentally measured and numerically simulated. Both approaches report a specific adsorption of halide anions at the cationic bilayer. The adsorption is enhanced for higher content of DOTAP in DOPC/DOTAP mixtures and for larger anions (Br  and ClO 4  ). The nonmonotonic dependence of the lipid headgroup mobility, determined using time-dependent fluorescence shifts of Laurdan located at the bilayer carbonyl level, on the content of cationic lipid is preserved in all examined salt solutions. Its maximum, however, is shifted towards higher DOTAP concentrations in the row: NaF < NaCl < NaBr. The same ordering of salts is found for the simulated area per lipid and the measured rigidification of pure DOTAP bilayers. Simulations reveal that Br  strongly binds to the cationic headgroups of DOTAP neutralising the bilayer, which induces lateral inhomogeneities in the form of hydrophilic and hydrophobic patches at the membrane–water interface for pure DOTAP. In the equimolar DOPC/DOTAP mixture the neutralising effect of Br  results in bending of the PC headgroups to a bilayer-parallel orientation. F  , while attracted to the DOTAP bilayer, has an opposite effect to that of Br  , i.e. it increases local mobility at the lipid carbonyl level. We attribute this effect to the disruption of the hydrogen-bonded structure of the molecules of lipids and water caused by the presence of the adsorbed F  . 1 Introduction Lipid bilayers are supramolecular aggregates with a complex, yet well-defined struc- ture. 1 Being the fundamental structural units of all biological membranes they are often used as model systems in science. The self-assembly and the maintenance of the organization of the amphiphilic molecules of lipids in the bilayers is governed by the hydrophobic effect. 2 Yet, number of weak interactions with macromolecules as well as with salt ions affect the physical and biological properties of lipid membranes. 3 Specific ionic effects investigated in lipid membranes are often related to either the direct or reversed Hofmeister series. 4,5 The studies were usually limited a J. Heyrovsk y Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, v. v. i., Dolej skova 3, 18223 Prague 8, Czech Republic b Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Center for Biomolecules and Complex Molecular Systems, Flemingovo n  am. 2, 16610 Prague 6, Czech Republic c Rudjer Bo skovi c Institute, Division of Organic Chemistry and Biochemistry, POB 180, HR- 10002 Zagreb, Croatia ART  C2FD20098H 1 5 10 15 20 25 30 35 40 45 50 55 This journal is ª The Royal Society of Chemistry 2012 Faraday Discuss., 2012, 160, 1–18 | 1 PAPER 160/19 www.rsc.org/faraday_d | Faraday Discussions