A novel perspective on the regulation of cardiac cell beating: cardiac cell under mechanical stimulation acts as "cell activation button" to activate adjacent cardiac cell.

The regulation of cardiac cell beating is of great significance for understanding cardiac coordination mechanisms and the treatment of cardiovascular diseases. Inspired by this natural "cell regulates cell" mode in which sinoatrial node cells regulate atrial myocytes, this study presented a novel method to replicate this behavior in vitro through mechanical stimulation. Primary cardiac cells from Sprague-Dawley rats were isolated, cultured in 2D substrates, and applied to precise mechanical stimulation by developing a micro-manipulation platform. We demonstrated that a mechanical probe can act as an external activation device for quiescent cardiac cells, transforming them into "activation cells" capable of activating adjacent "target cells" through bioelectrical coupling. Calcium imaging with Fluo-4 probes revealed that this "cell activates cell" mechanism relies on mechano-electric feedback and calcium-mediated signal propagation via cell junctions. Our findings provide a non-destructive strategy to regulate target cardiac cell, deepen insights into the mechanical modulation of intercellular communication, and offer a framework for studying arrhythmias linked to abnormal cell-cell communication. This work combined mechanical intervention with biological signaling, advancing potential applications in cardiovascular therapeutics.