An Integrated Optogenetic and Bioelectronic Platform for Regulating Cardiomyocyte Function

用于调节心肌细胞功能的集成光遗传学和生物电子平台

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作者:Olurotimi A Bolonduro, Zijing Chen, Yan-Ru Lai, Megan Cote, Akshita A Rao, Haitao Liu, Emmanuel S Tzanakakis, Brian P Timko

Abstract

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 μW/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 closed-loop feedback systems, with potential applications for cardiac regulation including arrhythmia diagnosis and intervention.

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