This study shows that coupling to designed plasmonic nanoparticles can modulate the electrophysiological function of proteins in living mammalian cells. Nanostar-shaped particles, that are robust to biological noise, are designed to enable near-field-coupling to plasma membrane-localized mutated Archaerhodopsin proteins in live cells. The coupled rhodopsins exhibit enhanced fluorescence and an increased response speed to membrane voltage. Incorporating this plasmonic enhancement into a Markov chain photocycle model of the Archaerhodopsin mutant QuasAr6a, shows an increased fluorescence emission rate and manipulation of the protein dynamics through a combination of photocycle transition rate enhancements. The results show an improvement in fluorescence and voltage-response dynamics of the functional QuasAr6a Archaerhodopsin mutant, beyond what has been achievable through genetic engineering. This opens up possibilities for engineering the biological functionality of proteins through plasmonics: manipulating protein photocycles could improve light sensitivity, change optogenetic applications, and lead to fluorescent biosensors with enhanced dynamics.
Locarno et al. (2026) studied this question.