Small amphiphilic molecules, such as ethanol, disturb the structure of lipid bilayer membranes to increase the membrane permeability, which is important for applications such as drug delivery, disinfection, and fermentation. To investigate how and the extent to which coexisting salts affect membrane disturbance, we performed molecular dynamics (MD) simulations on lipid bilayer membranes composed of zwitterionic lipids in aqueous ethanol solutions containing 0-631 mM NaCl, KCl, and KI salts. The addition of salts at low concentrations induced cationic adsorption on the lipid membrane, which competes with ethanol adsorption, thereby reducing the hydrogen bonds between ethanol and lipid molecules. This competitive adsorption mitigated the membrane disturbance and decreased the permeation of ethanol molecules into the membrane. In contrast, higher salt concentrations enhanced the membrane disturbance and permeability, which was caused by the salting-out of ethanol from the aqueous phase to the lipid bilayer. These conflicting effects appearing at different concentrations were stronger with the chloride salts than with the iodide salt. Among the two chloride salts, NaCl and KCl, the latter showed a greater enhancement in ethanol permeation at high concentrations. This seeming anti-Hofmeister salting-out behavior resulted from greater Na+ adsorption, preventing the ethanol-lipid interactions.
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