Fast and Local Mechanotransduction Control via Magnetic Nanoparticles: Mechanical Stimulation of Auditory Cells

Abstract

Converting a mechanical force into an electrochemical signal is a fundamental physiological process that underlies a number of senses, including touch, balance, proprioception, and hearing. Mechanosensitive ion channels play a crucial role in this process, switching into the open state when subjected to a mechanical stimulus which can take the form of stretch, pressure, or twist, and thus allowing an influx of ions into the cell. Although there has been much interest in understanding and controlling the mechanotransduction process, the development of appropriate tools with precise spatiotemporal control has posed challenges.We develop a technique to actuate mechanosensitive cells in a fast, reversible, and localized fashion and we test this method on auditory hair cells from the Bullfrog's sacculus. Cube-shaped magnetic nanoparticles are conjugated to Concanavalin A to bind to the hair bundle's surface. An electromagnetic probe then applies a calibrated magnetic force on pN scale on the particles, inducing a mechanical entrainment of the hair bundle at frequencies up to 10kHz. Such mechanical stimulation triggers the switching of ion channels from open to closed state, with the concomitant Calcium influx into the cell during the open state. Such influx is observed using fluorescent Calcium indicators. Moreover, the magnetic force stimulus can be designed to be complex and non-periodic, in order to probe specific nonlinear properties of the biological system.Our technique is applicable not only to the auditory system but to a broad range of sensory systems with mechanosensitive channels. The utilization of a controlled magnetic field, to which biological tissue is transparent, can be beneficial for remote and non-invasive stimulation of a wide range of biological targets.