Although
multiple forms of dimers have been described for GPCR,
their dynamics and function are still controversially discussed field.
Fluorescence microscopy allows GPCR to be imaged within their native
context; however, a key challenge is to site-specifically incorporate
reporter moieties that can produce high-quality signals upon formation
of GPCR dimers. To this end, we propose a supramolecular sensor approach
to detect agonist-induced dimer formation of μ-opioid receptors
(μORs) at the surface of intact cells. With the macrocyclic
host cucurbit[7]uril and its guest hemicyanine dye tethered to aptamer
strands directed against the histidine residues, the sensing module
is assembled by host–guest complexation once the histidine-tagged
μORs dimerize and bring the discrete supramolecular units into
close proximity. With the enhanced sensitivity attributed by the “turn-on”
fluorescence emission and high specificity afforded by the intermolecular
recognition, in situ visualization of dynamic GPCR dimerization was
realized with high precision, thereby validating the supramolecular
sensing entity as a sophisticated and versatile strategy to investigate
GPCR dimers, which represent an obvious therapeutic target