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.

中文翻译：

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使用工程化的听觉感知蛋白对细胞活性进行声波调制。

对不同外部刺激有反应的生物分子可以远程控制转基因细胞。我们在这里报告了一种超声生成方法，可以通过聚焦超声刺激来操纵靶细胞的活动。该系统需要源自工程听觉蛋白prestin的超声响应蛋白。小鼠prestin的异源表达包含两个平行的氨基酸取代，N7T和N308S，它们常存在于来自回声定位物种的prestins中，从而赋予转染的哺乳动物细胞以感知超声的能力。Prestin（N7T，N308S）转染后，低频低压超声脉冲可有效诱发细胞钙反应。此外，脉冲超声还可以无创地刺激表达prestin（N7T，N308S）位于小鼠大脑的深部区域。我们的研究描述了工程化的听觉感知蛋白如何引起哺乳动物细胞感知超声刺激。此外，我们的超声治疗工具将作为深层组织无创治疗的新策略。