Understanding interactions of calcium with lipid membranes at the molecular level is of great importance 
in light of their involvement in calcium signaling, association of proteins with cellular membranes, and 
membrane fusion. We quantify these interactions in detail by employing a combination of spectroscopic 
methods with atomistic molecular dynamics simulations. Namely, time-resolved fluorescent spectroscopy of 
lipid vesicles and vibrational sum frequency spectroscopy of lipid monolayers are used to characterize 
local binding sites of calcium in zwitterionic and anionic model lipid assemblies, while dynamic light 
scattering and zeta potential measurements are employed for macroscopic characterization of lipid vesicles 
in calcium-containing environments. To gain additional atomic-level information, the experiments are 
complemented by molecular simulations that utilize an accurate force field for calcium ions with scaled 
charges effectively accounting for electronic polarization effects. We demonstrate that lipid membranes 
have substantial calcium-binding capacity, with several types of binding sites present. Significantly, 
the binding mode depends on calcium concentration with important implications for calcium buffering, 
synaptic plasticity, and protein-membrane association.