Ultrasound mediated control of neurons and immune cells

Abstract

Ultrasound holds great promise for realizing noncontact stimulation and control of cell function. Here, we will present our ongoing efforts in controlling cell responses using two distinct approaches. The first is based on engineered cytotoxic immune cells with thermal switches, where closed-loop controlled MRgFUS-hyperthermia (20-mins at 42 °C) is employed to drive the local production of key transgenes and potentiate anti-tumor responses in brain tumors. The responses are assessed using bioluminescence, cell viability, and cell cytotoxicity assays. The second is based on US pulse sequences designed to promote mechanical effects on cultured cells with the goal to decode US neuromodulation. For our investigations, we employed a high throughput ultrasonic platform designed to monitor and locally control sound and vibration in combination DRG sensory neurons. The later are the most sensitive neuronal type to mechanical stretch and present an excellent experimental system to examine and identify mechanosensitive ion channels sensing sonication-induced membrane stretch. Cell responses are quantified and analyzed for different pulse durations and amplitude, cell culture conditions, and degassing protocols. Together, our findings show that ultrasound thermal and mechanical effects can be employed to control the function of different cell types, albeit cells with thermal switches provide more robust responses.