Cell-to-cell interactions are key to many biological processes in normal development as well as in diseases, but getting a handle on them in vivo has been problematic, as most platforms provide static readouts and are unable to follow dynamic processes. Zhao et al. describe an approach to hook up live cells to a fluorescent aptamer probe, allowing such interactions to be followed in real time. The researchers combined fluorescence resonance energy transfer (FRET)-based sensors with intravital microscopy to image mesenchymal stem cells (MSC), which home to areas of inflammation, bone marrow and tumors. Starting with a previously described aptamer sensor for platelet-derived growth factor (PDGF, a chemoattractant of mesenchymal cells), they created a quench FRET sensor (Cy3/Cy5) that was attached to biotin, a cell-anchoring moiety. Attachment to cells involved a simple three-step process, depositing 21,000 molecules on the surface of each MSC. After showing that the engineered MSCs sensed PDGF produced by cultured breast cancer cells in vitro, the researchers used confocal and multiphoton imaging to track the migration of the sensors to bone marrow 24 hours after injection into mice. (Nat. Nanotechnol. 6, 524–531, 2011)