Informace o publikaci
Mechanobiological distinction of focal and conductive arrhythmias by atomic force microscopy
| Autoři | |
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| Rok publikování | 2026 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Přiložené soubory | |
| Popis | Accurate detection of conduction disorders is essential for assessing arrhythmogenic risk in drug development and cardiovascular safety. Traditional biosensors often miss the mechanical aspects of cardiomyocyte function and the stochastic nature of arrhythmias. To overcome these limitations, we developed a dual-organoid biosensor using human pluripotent stem cell-derived cardiac organoids and Atomic Force Microscopy (AFM) to measure contractile motion in both vertical (DFL) and lateral (LF) directions. This setup enhances robustness and offers distinction between focal and conductive arrhythmias. Methods and Results AFM cantilever was placed on closesly cultivated organoid twins (preseting conductive bridge between the clusters and synchornized contraction after four days of co-cultivation). Recorded were DFL and LF deflections at 100 Hz, followed by Z-score normalization. Linear regression of LF on DFL was used to derive residual variance as a marker of conduction stability. The system distinguished synchronized controls from unsynchronized clusters, the latter showing higher residual variance (SD: 0.89 vs. 0.28). Electrophysiogical standard Tyrod solution 1,8mM was having midrange SD: 0,56. Pharmacological validation showed that salbutamol (10 nM) and aminophylline (1 mM) reduced variance (SD: 0.43 and 0.32), indicating improved conduction. Heptanol, a connexin blocker, increased variance (SD: 0.87), similar to the unsynchronized group (SD: 0.94). Lidocaine decreased variance dose-dependently compared to Tyrod solution (SD: 0.51), reflecting its antiarythmic effect on conduction. Conclusion: The dual-organoid platform effectively detects and quantifies arrhythmic events and drug responses, capturing both mechanical and stochastic features of conduction disorders. It offers a sensitive, physiologically relevant tool for preclinical cardiotoxicity screening. From pilot data is the most interesting fact that Aminophylline has stabilizing effect in proposed conduction evaluating system, thus its known arrythmogenic potential has probably more focal character. Funded by the Next Generation EU, National Institute for Research of Metabolic and CV Diseases EXCELES LX22NPO5104, CresPulse 101214165 HORIZON-EIC-2024 TRANSITION and Czech Science Foundation GACR 26-22811S |
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