Calcium binding and head group dipole angle in phosphatidylserine-phosphatidylcholine bilayers

Manipulating the plasma membrane, the gateway to the cell interior, with chemical and physical agents for genetic and pharmacological therapy, and understanding the interactions of lipid membrane components with proteins and other structural and functional elements of the cell, require a detailed biomolecular membrane model. We report here progress along one path toward such a model: molecular dynamics simulations of mixed, zwitterionic-anionic, asymmetric phospholipid bilayers with monovalent and divalent cations. With phosphatidylcholine/phosphatidylserine systems, we identify temporal and concentration boundaries for equilibration of calcium with the bilayer and saturation of the calcium capacity of the membrane, we demonstrate the electrostatic- and entropic-driven associations of calcium and sodium ions with polar groups in the bilayer interface region, expressed in spatial distribution profiles and in changes in the orientation of the phospholipid head groups, and we describe for the first time simulations of dynamic, calcium-mediated adjustments in the conformation of mixed phospholipid species coresident in the same leaflet of the bilayer. The results are consistent with experimental observations and point the way to further refinement and increased realism of these molecular models.