Curvature Matters: Modeling Calcium Binding to Neutral and Anionic Phospholipid Bilayers

In this work, the influence of membrane curvature on the Ca²⁺ binding to phospholipid bilayers is investigated by means of molecular dynamics simulations. In particular, we compared Ca²⁺ binding to flat, elastically buckled, or uniformly bent zwitterionic and anionic phospholipid bilayers. We demonstrate that Ca²⁺ ions bind preferably to the concave membrane surfaces in both types of bilayers. We also show that the membrane curvature leads to pronounced changes in Ca²⁺ binding including differences in free ion concentrations, lipid coordination distributions, and the patterns of ion binding to different chemical groups of lipids. Moreover, these effects differ substantially for the concave and convex membrane monolayers. Comparison between force fields with either full or scaled charges indicates that charge scaling results in reduction of the Ca²⁺ binding to curved phosphatidylserine bilayers, while for phosphatidylcholine membranes, calcium binds only weakly for both force fields.