Cell surface receptors account for vast majority of targets for therapeutic biologics. While mechanistic and structural studies have concentrated on the ligand-engaged, activated forms of the receptors, little information is available on the resting, inactive conformation of the receptors in the context of cell membrane. How receptors “rest” on the cell membrane has direct implication to their autoinhibition mechanism and thus to the development of agonistic or antagonistic antibodies for therapeutic applications. Historically, the pre-ligand state, or the resting state of single-pass transmembrane receptors, has been extremely difficult to visualize due to technical challenges of working with proteins in the context of lipid bilayer. My research program integrates structural biology, cell biology, and nanotechnology to fill the long-standing knowledge gaps in receptor biology such as receptor preligand clustering, receptor antoinhibition, and the active roles of transmembrane domain in receptor signaling.