The Vibration Behavior of Sub-Micrometer Gas Vesicles in Response to Acoustic Excitation Determined via Laser Doppler Vibrometry

The ability to monitor sub‐micrometer gas vesicles' (GVs) vibration behavior to nonlinear buckling and collapse using laser Doppler vibrometry is reported, providing a precise noncontact technique for monitoring the motion of sub‐micrometer objects. The fundamental and first harmonic resonance frequencies of the vesicles are found to be 1.024 and 1.710 GHz, respectively. An interparticle resonance is furthermore identified at ≈300 MHz, inversely dependent upon the agglomerated GV size of around 615 nm. Most importantly, the vesicles amplify and broaden input acoustic signals at far lower frequencies—for example, 7 MHz—associated with medical and industrial applications, and they are found to transition from a linear to nonlinear response at 150 kPa and to collapse at 350 kPa or greater

The Vibration Behavior of Sub-Micrometer Gas Vesicles in Response to Acoustic Excitation Determined via Laser Doppler Vibrometry

The ability to monitor sub‐micrometer gas vesicles' (GVs) vibration behavior to nonlinear buckling and collapse using laser Doppler vibrometry is reported, providing a precise noncontact technique for monitoring the motion of sub‐micrometer objects. The fundamental and first harmonic resonance frequencies of the vesicles are found to be 1.024 and 1.710 GHz, respectively. An interparticle resonance is furthermore identified at ≈300 MHz, inversely dependent upon the agglomerated GV size of around 615 nm. Most importantly, the vesicles amplify and broaden input acoustic signals at far lower frequencies—for example, 7 MHz—associated with medical and industrial applications, and they are found to transition from a linear to nonlinear response at 150 kPa and to collapse at 350 kPa or greater

Biomolecular Ultrasound and Sonogenetics

Visualizing and modulating molecular and cellular processes occurring deep within living organisms is fundamental to our study of basic biology and disease. Currently, the most sophisticated tools available to dynamically monitor and control cellular events rely on light-responsive proteins, which are difficult to use outside of optically transparent model systems, cultured cells, or surgically accessed regions owing to strong scattering of light by biological tissue. In contrast, ultrasound is a widely used medical imaging and therapeutic modality that enables the observation and perturbation of internal anatomy and physiology but has historically had limited ability to monitor and control specific cellular processes. Recent advances are beginning to address this limitation through the development of biomolecular tools that allow ultrasound to connect directly to cellular functions such as gene expression. Driven by the discovery and engineering of new contrast agents, reporter genes, and bioswitches, the nascent field of biomolecular ultrasound carries a wave of exciting opportunities

Acoustically Detonated Biomolecules for Genetically Encodable Inertial Cavitation

Recent advances in molecular engineering and synthetic biology have made it possible for biomolecular and cell-based therapies to provide highly specific disease treatment. However, both the ability to spatially target the action of such therapies, and their range of effects on the target tissue remain limited. Here we show that biomolecules and cells can be engineered to deliver potent mechanical effects at specific locations inside the body under the direction of focused ultrasound. This capability is based on gas vesicles, a unique class of air-filled protein nanostructures derived from buoyant photosynthetic microbes. We show that low-frequency ultrasound can convert these nanoscale biomolecules into micron-scale cavitating bubbles, as demonstrated with acoustic measurements and ultrafast optical microscopy. This allows gas vesicles targeted to cell-surface receptors to serve as remotely detonated cell-killing agents. In addition, it allows cells genetically engineered to express gas vesicles to be triggered with ultrasound to lyse and release therapeutic payloads. We demonstrate these capabilities in vitro, in cellulo, and in vivo. This technology equips biomolecular and cellular therapeutics with unique capabilities for spatiotemporal control and mechanical action