Genetically encoded nanostructures enable acoustic manipulation of engineered cells
The ability to mechanically manipulate and control the spatial arrangement of biological materials is a critical capability in biomedicine and synthetic biology. Ultrasound has the ability to manipulate objects with high spatial and temporal precision via acoustic radiation force, but has not been used to directly control biomolecules or genetically defined cells. Here, we show that gas vesicles (GVs), a unique class of genetically encoded gas-filled protein nanostructures, can be directly manipulated and patterned by ultrasound and enable acoustic control of genetically engineered GV-expressing cells. Due to their differential density and compressibility relative to water, GVs experience sufficient acoustic radiation force to allow these biomolecules to be moved with acoustic standing waves, as demonstrated within microfluidic devices. Engineered variants of GVs differing in their mechanical properties enable multiplexed actuation and act as sensors of acoustic pressure. Furthermore, when expressed inside genetically engineered bacterial cells, GVs enable these cells to be selectively manipulated with sound waves, allowing patterning, focal trapping and translation with acoustic fields. This work establishes the first genetically encoded nanomaterial compatible with acoustic manipulation, enabling molecular and cellular control in a broad range of contexts.
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Jul. 6, 2019. The authors thank James Friend and Aditya Vasan for helpful discussion, Hunter Davis for help with fluorescence microscopy, Zhiyang Jin for assistance with bacteria protein expression, Gabrielle Ho for assistance with electron microscopy, and Xiaozhe Ding for contribution to initial experiments. This work was funded by the National Institutes of Health (R01EB018975 to MGS), the Pew Scholarship in the Biomedical Sciences (to MGS) and the Packard Fellowship in Science and Engineering (to MGS). DW was supported by a Medical Engineering Amgen Fellowship. DB was supported by Newton International Fellowships (NF 161508). DMaresca was supported by the Human Frontiers Science Program Cross-Disciplinary Fellowship. MPA was supported by A*STAR. Author Contributions: DW, MGS, DB, and DMaresca conceived the study. DW and DB designed, planned, and conducted the experiments. DW, CC, and DRM designed and fabricated the acoustic devices. DW and DMalounda prepared the samples. DMaresca and MPA contributed to experiments. DW analyzed the data. DW and MGS wrote the manuscript with input from all authors. MGS supervised the research. The authors declare no competing financial interests.
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