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
Institute of Molecular Medicine , National Tsing Hua University , Hsinchu 300 , Taiwan.
Department of Biomedical Engineering and Environmental Sciences , National Tsing Hua University , Hsinchu 300 , Taiwan.
Nano Lett. 2020 Feb 12;20(2):1089-1100. doi: 10.1021/acs.nanolett.9b04373. Epub 2020 Jan 2.
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.
能够响应不同外部刺激的生物分子可实现对转基因细胞的远程控制。我们在此报告一种声遗传学方法，该方法可通过聚焦超声刺激来操纵靶细胞活性。该系统需要一种源自工程化听觉传感蛋白（prestin）的超声响应蛋白。含有两个平行氨基酸取代（N7T和N308S）的小鼠prestin的异源表达赋予了转染的哺乳动物细胞感知超声的能力，这两个取代在回声定位物种的prestin中经常出现。在用prestin（N7T，N308S）转染后，低频低压超声脉冲能有效诱发细胞钙反应。此外，脉冲超声还可以非侵入性地刺激小鼠大脑深部区域表达prestin（N7T，N308S）的靶神经元。我们的研究描述了一种工程化听觉传感蛋白如何使哺乳动物细胞感知超声刺激。此外，我们的声遗传学工具将作为深部组织无创治疗的新策略。
