Biomolecular actuators for genetically selective acoustic manipulation of cells

Abstract

The ability to physically manipulate specific cells is critical for the fields of biomedicine, synthetic biology, and living materials. Ultrasound has the ability to manipulate cells with high spatiotemporal precision via acoustic radiation force (ARF). However, because most cells have similar acoustic properties, this capability is disconnected from cellular genetic programs. Here, we show that gas vesicles (GVs)—a unique class of gas-filled protein nanostructures—can serve as genetically encodable actuators for selective acoustic manipulation. Because of their lower density and higher compressibility relative to water, GVs experience strong ARF with opposite polarity to most other materials. When expressed inside cells, GVs invert the cells’ acoustic contrast and amplify the magnitude of their ARF, allowing the cells to be selectively manipulated with sound waves based on their genotype. GVs provide a direct link between gene expression and acoustomechanical actuation, opening a paradigm for selective cellular control in a broad range of contexts.

Ultrasound meets the cell membrane: for enhanced endocytosis and drug delivery

“…Recently, genes that encode gas vesicles could be transfected into the cells of interest to achieve a certain number of microbubbles, which has excellent potential in USassisted precision medicine. 112,113 Besides, the US penetration ability is mainly related to its frequency, tissue attenuation coefficient, and patient heterogeneity. And the tissue penetration depth usually limits the enhancement of ultrasound-induced endocytosis.…”

“…The GVs could reverse the acoustic contrast of the cell and amplify the acoustic radiation force (ARF) on the cell, allowing them to move in response to variations in pressure, and provide a new strategy for selective acoustic manipulation. 113…”

Acoustic Trapping and Manipulation of Hollow Microparticles under Fluid Flow Using a Single-Lens Focused Ultrasound Transducer

“…There are other materials such as polymeric particles , and gas vesicles , in the literature with negative acoustic contrast factor. It would be worthwhile to compare the values of the expected negative contrast factor and range of acoustic radiation force between them.…”

“…Additionally, if this method were to be applied to drug carrier systems, then it would be necessary to test its performance in biological fluids, such as blood. 54,55 There are other materials such as polymeric particles 56,57 and gas vesicles 58,59 in the literature with negative acoustic contrast factor. It would be worthwhile to compare the values of the expected negative contrast factor and range of acoustic radiation force between them.…”

Gas Vesicle–Blood Interactions Enhance Ultrasound Imaging Contrast

“…GVs comprise a 2 nm thick protein shell that excludes liquid water but permits the dynamic exchange of gas, forming a thermodynamically stable pocket of air with nanoscale dimensions . Acoustic waves are strongly scattered at this air–water interface, enabling GVs to produce robust ultrasound contrast when injected into the body − or expressed in engineered cells. , Furthermore, they are resilient to repeated insonation, easily tailored to target molecular markers − or respond to biological functions, , and have growing applications in therapeutic ultrasound, , optical imaging, , and magnetic resonance imaging. , To effectively incorporate these capabilities into an injectable agent, a deeper understanding of in vivo GV behavior is needed.…”