Cardiac myocyte microtissue aggregates broadcast local field potentials

Abstract

Muscle tissue has been exploited as a living biopotential amplifier to facilitate transduction of peripheral nerve signals into prosthetic control in patients with limb amputation. Here we sought to address the question of whether microscopically small volumes of muscle tissue could effectively broadcast field potentials to electrodes not immediately in contact with that tissue. Cardiac myocytes were grown as three-dimensional aggregates containing 105 cells comprising a volume of approximately 0.065 mm3 (~500 m in diameter) atop multi-electrode arrays. In addition to the expected spontaneous contraction potentials detected using electrodes in direct contact with the myocytes, potentials could also be detected on distant electrodes not contacting the aggregates. Specifically, while both dissociated and aggregated cardiac myocyte cultures generated spontaneous contractions that could easily be recorded from underlying multi-electrode arrays, only aggregated myocyte cultures generated signals detectable several millimeters away by the electrode grid floating in media. This confirmed the ability of micro-volumes of aggregated muscle tissue to broadcast readily detectible signals. The amplitude of the potentials generated by the aggregates decreased exponentially with distance. The aggregates were sensitive to pharmacologic modification with isoproterenol increasing contraction rate. Simultaneous recordings with electrodes in physical contact to the aggregate and with electrodes several millimeters away revealed that the aggregates function as amplifiers and low-pass filters. This study lays the groundwork for forging myocyte aggregates as \"living amplifiers\" for long-term neural recording in brain-computer interfaces to treat neurological disease and injury.