An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function

We report an integrated optogenetic and bioelectronic platform for stable and long-term modulation and monitoring of cardiomyocyte function in vitro. Optogenetic inputs were achieved through expression of a photoactivatable adenylyl cyclase (bPAC), that when activated by blue light caused a dose-dependent and time-limited increase in autonomous cardiomyocyte beat rate. Bioelectronic readouts were achieved through an integrated planar multi-electrode array (MEA) that provided real-time readouts of electrophysiological activity from 32 spatially-distinct locations. Irradiation at 27 W/mm2 resulted in a ca. 14% increase in beat rate within 20-25 minutes, which remained stable for at least 2 hours. The beating rate could be cycled through repeated "on" and "off" states, and its magnitude was a monotonic function of irradiation intensity. Our integrated platform opens new avenues in bioelectronic medicine, including closedloop feedback systems, with potential applications for cardiac regulation including arrhythmia diagnosis and intervention. TeaserA system that integrates optogenetic stimulation and bioelectronic recording capabilities allows for on-demand regulation of cardiac cell function.