Sonogenetic Modulation of Cellular Activities Using an Engineered Auditory-Sensing Protein

Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an...

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Published inNano letters Vol. 20; no. 2; pp. 1089 - 1100
Main Authors Huang, Yao-Shen, Fan, Ching-Hsiang, Hsu, Ning, Chiu, Nai-Hua, Wu, Chun-Yao, Chang, Chu-Yuan, Wu, Bing-Huan, Hong, Shi-Rong, Chang, Ya-Chu, Yan-Tang Wu, Anthony, Guo, Vanessa, Chiang, Yueh-Chen, Hsu, Wei-Chia, Chen, Linyi, Pin-Kuang Lai, Charles, Yeh, Chih-Kuang, Lin, Yu-Chun
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 12.02.2020
Subjects
Animals
Brain - metabolism
Echolocation
Hearing - genetics
Hearing - physiology
Humans
Mice
Molecular Motor Proteins - chemistry
Molecular Motor Proteins - genetics
Neurons - chemistry
Neurons - metabolism
Protein Engineering - methods
Ultrasonic Waves
neuromodulation
Sonogenetics
mammalian cells
focused ultrasound
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Summary:Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterologous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin­(N7T, N308S). Moreover, pulsed ultrasound can also noninvasively stimulate target neurons expressing prestin­(N7T, N308S) in deep regions of mouse brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, our sonogenetic tools will serve as new strategies for noninvasive therapy in deep tissues.
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ISSN:1530-6984
1530-6992
1530-6992
DOI:10.1021/acs.nanolett.9b04373