The functional analysis of transmembrane receptor proteins is frequently hampered by the difficulty to produce sufficiently homogeneous receptor preparations that preserve the physiological biomembrane integration of the receptor protein. To improve the receptor protein density in the lipid bilayer and to maintain the physiological lipid−protein environment, a novel method has been established that enables the selective integration of transmembrane receptors into a virus-like particle (VLiP). Here we have studied the binding of tetramethylrhodamine-labeled endothelin-1 (TMR-ET-1) to VLiP-integrated endothelin A receptor (ETAR) by fluorescence fluctuation spectroscopy. The concentration of TMR-ET-1 was determined by fluorescence correlation spectroscopy (FCS). These measurements also confirmed that the free ligand is monomeric in solution in our experiments. Fluorescence intensity distribution analysis (FIDA) was used to quantify the fraction of ligands bound to ETARs in the VLiPs. For the interaction betw...