The recent appearance of the tethered vesicle assembly in literature has generated much attention because the assembly possesses great potential as a biomimetic model membrane platform to study membrane proteins and constituents and has potential applications in high throughput biomolecule-based sensors, molecular separation systems, and “lab-on-a-chip” devices. This molecular assembly also overcomes the major limitations of previous model membrane systems by providing a fluid, defect-free membrane for membrane proteins while avoiding deleterious protein-substrate interactions. We exploited the location of the assembly on a planar, solid substrate by employing a powerful surface-sensitive technique, quartz crystal microbalance with dissipation monitoring (QCM-D), to quantify binding of antibodies to antigens displayed on the surface of the tethered liposomes. This was achieved through the application of appropriate viscoelastic models for QCM-D data as well as traditional biochemical assays. This work demonstrates the utility of both the assembly as well as the technique to probe binding events and enables interpretation of QCM-D responses for interactions between membrane proteins and their ligands.