Abstract
Bio-pacemakers offer a potential alternative to electronic devices, yet their stable implementation at cellular and tissue levels remains unresolved. In this computational study, we aimed to investigate possible effects of the electrotonic interaction between cardiac cells and the spatial distribution of the bio-pacemaker on the initiation and conduction of cardiac pacemaking action potentials to surrounding quiescent cardiac tissues. Simulation results demonstrated that (i) a combination of weak gap junctional electrical coupling among PMs; and (ii) rectified coupling arising from heterotypic gap junction expressions between the PM and ventricle yielded the best stable and robust bio-pacemaker for pacing and driving surrounding ventricular tissue. Furthermore, Isolated or septal placement improved ventricular pacing efficacy. This study adopts a digital health approach, providing an important theoretical foundation for the simulation of new clinical therapies.
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This study is based on computational simulations, and all data can be derived analytically from the equations presented. The relevant mathematical formulations and derivation steps are provided in the Supplementary Materials.
Code availability
The computational code used in this study was developed for research purposes and is available from the corresponding author upon reasonable request.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (NSFC) under Grant No. 62133009 and No. 61702026, and the Open Project Program of State Key Laboratory of Virtual Reality Technology and Systems, Beihang University, under Grant No. VRLAB2024A05.
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Conceptualisation: Qince Li, Henggui Zhang; Data curation: Yacong Li, Dong Sui; Formal analysis: Yacong Li, Xiangyun Bai; Funding acquisition: Yacong Li, Dong Sui, Qince Li; Investigation: Yacong Li, Dong Sui, Deyan Yang; Methodology: Yacong Li, Jun Liu, Xiangyun Bai, Qince Li; Project administration: Lei Ma, Kuanquan Wang, Henggui Zhang; Resources: Yacong Li, Qince Li, Lei Ma; Software: Yacong Li, Xiangyun Bai, Dong Sui; Supervision: Kuanquan Wang, Henggui Zhang; Validation: Yacong Li, Deyan Yang; Visualisation: Yacong Li, Dong Sui; Writing – original draft: Yacong Li, Jun Liu, Xiangyun Bai, Dong Sui; Writing – review & editing: Qince Li, Lei Ma, Kuanquan Wang, Henggui Zhang.
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Li, Y., Liu, J., Bai, X. et al. Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells. npj Syst Biol Appl (2026). https://doi.org/10.1038/s41540-025-00646-3
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DOI: https://doi.org/10.1038/s41540-025-00646-3
