The lateral organization of lipids and membrane receptors in the plasma membrane (PM) is connected to a large variety of biological processes including immune response, cell-cell communication, membrane trafficking and some bacterial and viral infections. A growing amount of data suggest that chemically selective assemblies of lipids and proteins can exist in cellular membranes and that they have a role in several biological contexts. The characterization of such domains in vivo has proved so far to be very challenging due to their small size and dynamic nature and therefore requires the design of innovative, versatile and effective experimental approaches. On the other hand, the improvement of existing membrane physical models is also of vital importance for the full understanding of cell membrane function through the biophysical characterization of lipid-protein interactions. In the first part of my presentation, I will describe a combination of Atomic force microscopy (AFM) and Fluorescence Correlation Spectroscopy (FCS) that proved particularly useful for the characterization of structural and dynamic properties of artificial model PM containing "raft" and ceramide domains. In the second part, I will describe novel and advanced asymmetric model bilayers (e.g. asymmetric giant unilamellar vesicles or GUVs) which mimic the compositional lipid asymmetry of cellular PM.