Genetically encoded mediators for sonogenetics and their applications in neuromodulation

Abstract

Sonogenetics is an emerging approach that harnesses ultrasound for the manipulation of genetically modified cells. The great penetrability of ultrasound waves enables the non-invasive application of external stimuli to deep tissues, particularly advantageous for brain stimulation. Genetically encoded ultrasound mediators, a set of proteins that respond to ultrasound-induced bio-effects, play a critical role in determining the effectiveness and applications of sonogenetics. In this context, we will provide an overview of these ultrasound-responsive mediators, delve into the molecular mechanisms governing their response to ultrasound stimulation, and summarize their applications in neuromodulation.

Keywords: gas vesicles; mechanosensitive ion channels; prestin; sonogenetics; ultrasound.

Figure 1

US-induced bio-effects and sensing proteins in sonogenetics. Ultrasonic waves give rise to a variety of bio-effects including thermal effects, membrane cavitation, and the generation of mechanical forces to cellular components. The US-induced heating activates thermosensitive ion channels, resulting in ion influx. The US energy could covert to mechanical forces that induce membrane deflection or intramembrane cavitation and subsequently activate mechanosensitive ion channels to facilitate ion influx. The increase in membrane tension induces transmembrane voltage fluctuations, which can be sensed by prestin, triggering downstream calcium influx through its electromobility. Gas vesicles vibrate in response to acoustic pressures, improving membrane permeability for the influx of ions and membrane impermeable molecules. The US-induced mechanical force effects can be further intensified by gas vesicles, promoting ion influx through mechanosensitive ion channels. The ion influx resulting from the aforementioned mechanisms alters the membrane potential, ultimately leading to neuromodulation (Figure created by BioRender.com).