Calcium-Lipid Interactions Observed with Isotope-Edited Infrared Spectroscopy

Abstract Calcium ions bind to lipid membranes containing anionic lipids; however, characterizing the specific ion-lipid interactions in multicomponent membranes has remained challenging, as it requires nonperturbative lipid-specific probes. Here, using a combination of isotope-edited infrared spectroscopy and molecular dynamics simulations, we characterize the effects of a physiologically relevant (2 mM) Ca2+ concentration on zwitterionic phosphatidylcholine (PC) and anionic phosphatidylserine (PS) lipids in mixed lipid membranes. We show that Ca2+ alters hydrogen bonding between water and lipid headgroups by forming a coordination complex involving the lipid headgroups and water. These interactions distort interfacial water orientations and prevent hydrogen bonding with lipid ester carbonyls. We demonstrate experimentally that these effects are more pronounced for the anionic PS lipids than for zwitterionic PC lipids in the same membrane.