In-vivo programmable acoustic manipulation of genetically engineered bacteria

Ye Yang, Yaozhang Yang, Dingyuan Liu, Yuanyuan Wang, Minqiao Lu, Qi Zhang, Jiqing Huang, Yongchuan Li, Teng Ma (), Fei Yan () and Hairong Zheng ()
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Ye Yang: Chinese Academy of Sciences
Yaozhang Yang: Chinese Academy of Sciences
Dingyuan Liu: Chinese Academy of Sciences
Yuanyuan Wang: Chinese Academy of Sciences
Minqiao Lu: Chinese Academy of Sciences
Qi Zhang: Chinese Academy of Sciences
Jiqing Huang: Chinese Academy of Sciences
Yongchuan Li: Chinese Academy of Sciences
Teng Ma: Chinese Academy of Sciences
Fei Yan: Chinese Academy of Sciences
Hairong Zheng: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Acoustic tweezers can control target movement through the momentum interaction between an acoustic wave and an object. This technology has advantages over optical tweezers for in-vivo cell manipulation due to its high tissue penetrability and strong acoustic radiation force. However, normal cells are difficult to acoustically manipulate because of their small size and the similarity between their acoustic impedance and that of the medium. In this study, we use the heterologous expression of gene clusters to generate genetically engineered bacteria that can produce numerous sub-micron gas vesicles in the bacterial cytoplasm. We show that the presence of the gas vesicles significantly enhances the acoustic sensitivity of the engineering bacteria, which can be manipulated by ultrasound. We find that by employing phased-array-based acoustic tweezers, the engineering bacteria can be trapped into clusters and manipulated in vitro and in vivo via electronically steered acoustic beams, enabling the counter flow or on-demand flow of these bacteria in the vasculature of live mice. Furthermore, we demonstrate that the aggregation efficiency of engineering bacteria in a tumour is improved by utilizing this technology. This study provides a platform for the in-vivo manipulation of live cells, which will promote the progress of cell-based biomedical applications.

Date: 2023
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DOI: 10.1038/s41467-023-38814-w

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