Optical stimulation has enabled important advances in the study of brain function and other biological processes, and holds promise for medical applications ranging from hearing restoration to cardiac pace making. In particular, pulsed laser stimulation using infrared wavelengths >1.5 μm has therapeutic potential based on its ability to directly stimulate nerves and muscles without any genetic or chemical pre-treatment. However, the mechanism of infrared stimulation has been a mystery, hindering its path to the clinic. Here we show that infrared light excites cells through a novel, highly general electrostatic mechanism. Infrared pulses are absorbed by water, producing a rapid local increase in temperature. This heating reversibly alters the electrical capacitance of the plasma membrane, depolarizing the target cell. This mechanism is fully reversible and requires only the most basic properties of cell membranes. Our findings underscore the generality of pulsed infrared stimulation and its medical potential.

Ultrasound is among the most widely used non-invasive imaging modalities in biomedicine1, but plays a surprisingly small role in molecular imaging due to a lack of suitable molecular reporters on the nanoscale. Here we introduce a new class of reporters for ultrasound based on genetically encoded gas nanostructures from microorganisms, including bacteria and archaea. Gas vesicles are gas-filled protein-shelled compartments with typical widths of 45–250 nm and lengths of 100–600 nm that exclude water and are permeable to gas2, 3. We show that gas vesicles produce stable ultrasound contrast that is readily detected in vitro and in vivo, that their genetically encoded physical properties enable multiple modes of imaging, and that contrast enhancement through aggregation permits their use as molecular biosensors.

* The reported Toff for each variant is the lowest temperature at which fluorescence could be detected above noise. Tmax is the temperature at which fluorescence was maximal. Supplementary Table 2-Genetic constructs used in the study All plasmids were constructed using the pETDuet-1 backbone (EMD Biosciences) with the relevant thermal biosensor elements replacing multiple cloning sites 1 and 2.