Adsorption of metal cations to a cellular membrane changes
its properties, such as interactions with charged moieties
or the propensity for membrane fusion. It is, however,
unclear whether cells can regulate ion adsorption and
the related functions via locally adjusting their membrane
composition. We employed fluorescence techniques and
computer simulations to determine how the presence of
cholesterol  - a key molecule inducing membrane heterogeneity
- affects the adsorption of sodium and calcium to
zwitterionic phosphatidylcholine bilayers. We found that the
transient adsorption of sodium is dependent on the number
of phosphatidylcholine head groups, while the strong
surface binding of calcium is determined by the available
surface area of the membrane. Cholesterol thus does not
affect sodium adsorption and only plays an indirect role in
modulating the adsorption of calcium by increasing the total
surface area of the membrane. These observations also
indicate how lateral lipid heterogeneity can regulate various
ion-induced processes including adsorption of peripheral
proteins, nanoparticles, and other molecules to membranes.