动力蛋白
光遗传学
超声波
转染
细胞生物学
神经科学
化学
生物
耳蜗
毛细胞
生物化学
基因
医学
放射科
作者
Yao‐Shen Huang,Ching-Hsiang Fan,Nan‐Jung Hsu,Chun-Yao Wu,Chien-Chi Chang,Shi‐Rong Hong,Yaw-Jen Chang,Anthony Yan-Tang Wu,Vanessa Guo,Yueh-Chen Chiang,Wei-Chia Hsu,Nai-Hua Chiu,Linyi Chen,Charles Pin-Kuang Lai,Chih‐Kuang Yeh,Yu‐Chun Lin
摘要
Abstract Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. Chemogenetics and optogenetics, two tools that can control cellular activities via synthetic chemicals or photons, respectively, have been widely used to elucidate underlying physiological processes. These methods are, however, very invasive, have poor penetrability, or low spatiotemporal precision, attributes that hinder their use in therapeutic applications. 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. Heterogeneous 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 non-invasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mice brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, owing to the great penetration of low-frequency ultrasound (∼400 mm in depth), our sonogenetic tools will serve as new strategies for non-invasive therapy in deep tissues of large animals like primates.
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