Experimental observations indicate that the interaction between nanoparticles and lipid membranes varies according to the nanoparticle charge and the chemical nature of their protecting side groups. We report atomistic simulations of an anionic Au nanoparticle (AuNP−) interacting with membranes whose lipid composition and transmembrane distribution are to a large extent consistent with real plasma membranes of eukaryotic cells. To this end, we use a model system which comprises two cellular compartments, extracellular and cytosolic, divided by two asymmetric lipid bilayers. The simulations clearly show that AuNP− attaches to the extracellular membrane surface within a few tens of nanoseconds, while it avoids contact with the membrane on the cytosolic side. This behavior stems from several factors. In essence, when the nanoparticle interacts with lipids in the extracellular compartment, it forms relatively weak contacts with the zwitterionic head groups (in particular choline) of the phosphatidylcholine lipids. Consequently, AuNP− does not immerse deeply in the leaflet, enabling, e.g., lateral diffusion of the nanoparticle along the surface. On the cytosolic side, AuNP− remains in the water phase due to Coulomb repulsion that arises from negatively charged phosphatidylserine lipids interacting with AuNP−. A number of structural and dynamical features resulting from these basic phenomena are discussed. We close the article with a brief discussion of potential implications.