Plasmon Resonance Energy Transfer for Molecular-Scale Tracking Receptor Dimerization and Apoptosis at the Single-Cell Level

Plasmon resonance energy transfer (PRET) faces critical challenges in achieving precise molecular-scale distance control and non-perturbative operation within single live-cell environments, e.g., the inability to dynamically tune the donor-acceptor distance (<i>r</i>) at the single molecular dipole level. To overcome these bottlenecks, we designed a non-genetic, non-fluorescent PRET nanodevice integrating a single gold nanoparticle donor (ErbB3-targeting antibody@GNP), a single molecular dipole acceptor (ErbB2-targeting aptamer@TAMRA), and a programmable nucleic acid spacer (nTA). This spacer enables precise <i>in situ</i> control of <i>r</i> (2.7 nm vs 7.2 nm) on the single-living MCF-7 cell membrane. At <i>r</i> ≈ 2.7 nm (PRET-ON), ErbB2-ErbB3 heterodimerization occurs, suppressing apoptosis. At <i>r</i> ≈ 7.2 nm (PRET-OFF), receptor dissociation activates caspase-9-mediated apoptosis via suppression of the AKT pathway suppression. This distance-tunable single molecular dipole PRET nanodevice overcomes membrane fluidity constraints, eliminates photobleaching artifacts, and provides long-term, single-cell resolution, establishing a potential universal platform for spatiotemporally controlling receptor interactions and downstream signaling.