The study of biological function in intact organisms and the development of targeted cellular therapeutics necessitate methods to image and control cellular function in vivo. Technologies such as optogenetics serve this purpose in small, translucent specimens, but are limited by the poor penetration of light into deeper tissues. In contrast, non-invasive techniques such as ultrasound – while based on energy forms that penetrate tissue effectively – are not as effectively coupled to cellular function. Our work attempts to bridge this gap by engineering biomolecules with the appropriate physical properties to interact with sound waves, and to enhance the transport of engineered biomolecules into tissues such as the brain. In this talk, I will describe two classes of biomolecular acoustic actuators. One is based on genetically encodable air-filled protein nanostructures known as gas vesicles, which can be converted to free bubbles using low frequency ultrasound. This enables gas vesicles, and cells engineered to express them, to serve as targeted seeds for inertial cavitation, thereby combining molecular and cellular logic with strong mechanical action. The second class of actuators is based on temperature-dependent transcriptional regulators, which provide switch-like control of gene expression in response to small changes in temperature delivered by ultrasound. This allows us to use focused ultrasound to remote-control the function of engineered cells in vivo. In addition, I will describe our efforts to use ultrasound in combination with viral vectors and engineered receptors to provide spatially and cell-type specific non-invasive control over neural activity.