There are many image based approaches for studying receptor activation. Binding of fluorescently labeled ligands to the receptors on the plasma membrane, eventually followed by internalization of the ligand-receptor complex is one of them.

A more relevant method of studying receptor activation is to monitor the processes which follow activation of a receptor, such as internalization and endocytosis of activated receptors carrying a fluorescent tag.  This produces a more accurate readout with less false positives.

Another approach is based on signal molecule recruitment to activated receptor complexes. G protein coupled receptor (GPCR) activation, for example, can be studied by the binding of arrestin carrying a fluorescent protein tag followed by the formation of fluorescent clathrin-coated pits at the cell surface or fluorescent clathrin-coated vesicles in the cytoplasm.

One of the earliest structural changes observed in cells in response to many extracellular factors is membrane ruffling: the formation of motile cell surface protrusions containing a meshwork of newly polymerized actin filaments.

It is becoming clear that actin reorganization is an integral part of early signal transduction pathways, and that many signaling molecules interact with the actin cytoskeleton.