Sono-uncaging for Spatiotemporal Control of Chemical Reactivity

Photo-uncaging─the use of light to reveal the active part of a chemical compound by photolysis of a protecting group─has long been used to study and actuate biochemical processes. However, light scattering limits the applications of photo-uncaging in opaque specimens or tissues. Here, we introduce <i>sono-uncaging</i>, a process in which a chemical functional group becomes exposed upon the application of ultrasound, which can be applied and focused in optically opaque materials. We engineered gas vesicles (GVs), air-filled protein nanostructures sensitive to ultrasound, to contain cysteines on their concealed inner surface, hypothesizing that the application of ultrasound would collapse the GV shell and reveal the cysteines. The resulting SonoCage construct reacted with monobromobimane (mBBr), a fluorogenic, thiol-reactive molecule, only after treatment with ultrasound, establishing the sono-uncaging proof of concept. We then demonstrated the spatial patterning capability of sono-uncaging by embedding the SonoCages in an mBBr-containing hydrogel and creating fluorescent patterns with phased array ultrasound. This patterning could be accomplished using a diagnostic imaging transducer with mild ultrasound conditions. This work establishes sono-uncaging as a method for spatiotemporal control over chemical reactivity using widely available ultrasound technology.