Biology subjects

Fenton, F.

Publications and source records attributed to Fenton, F..

3 recordsLinked to original sources

bioRxiv2026

Real-Time GPU-Accelerated Digital Heart Twin: Integrating Bidirectional Interactions Between Living Optogenetic Monolayers and Computational Simulations

Reentrant arrhythmias are life-threatening cardiac events that are difficult to study due to limited experimental control over the complex circuit dynamics. We aimed to develop a real-time digital heart twin that allows in real-time dynamic manipulation of reentrant pathways in vitro using physiologically relevant simulations. We designed a closed-feedback loop system that couples a cultured cardiac monolayer with a two-dimensional computational simulation of cardiac tissue. The simulation, based on GPU-accelerated models (e.g., cellular automata), predicts wave propagation in real-time using the Abubu.js library. Optical mapping captures monolayer activation patterns, and simulation outputs are converted into light-based stimulation via optogenetics, using LEDs and microcontrollers to depolarize cardiac tissue. Our platform is capable of accurately detecting and responding to electrical waves in real-time, enabling interactive control of reentrant circuits. The system replaces traditional fixed-delay stimulation protocols with computationally guided interventions, better mimicking physiological conduction dynamics. This digital twin provides a novel and responsive method to study reentrant arrhythmias. Its integration of optical stimulation, real-time modeling, and tissue feedback enables the construction of user-defined reentry pathways under dynamic control. By merging computational and biological systems, this work introduces a versatile experimental framework for investigating arrhythmias. The platform may inform future control and anti-arrhythmic strategies and pave the way for personalized cardiac electrophysiology studies.

bioengineering↗

bioRxiv2024

Mechanism of Arrhythmogenesis Driven by Early After Depolarizations in Cardiac Tissue

Early-after depolarizations (EADs) are changes in the action potential plateau that can lead to cardiac arrhythmia. At the cellular level, these oscillations are irregular and change from beat to beat due to the sensitivity of voltage repolarization to subcellular stochastic processes. However, the behavior of EADs in tissue, where cells are strongly coupled by gap junctions, is less understood. In this study, we develop a computational model of EADs caused by a reduction in the rate of calcium-induced inactivation of the L-type calcium channel. We find that, as inactivation decreases EADs occur with durations varying randomly from beat to beat. In cardiac tissue, however, gap junction coupling between cells dampens these fluctuations, and it is unclear what dictates the formation of EADs. In this study we show that EADs in cardiac tissue can be modeled by the deterministic limit of a stochastic single-cell model. Analysis of this deterministic model reveals that EADs emerge in tissue after an abrupt transition to alternans, where large populations of cells suddenly synchronize, causing EADs on every other beat. We analyze this transition and show that it is due to a discontinuous bifurcation that leads to a large change in the action potential duration in response to very small changes in pacing rate. We further demonstrate that this transition is highly arrhythmogenic, as the sudden onset of EADs in cardiac tissue promotes conduction block and reentry. Our results highlight the importance of EAD alternans in arrhythmogenesis and suggests that ectopic beats are not required.

synthetic biology↗

bioRxiv2020

Generation of Monophasic Action Potentials and Intermediate Forms

The Monophasic Action Potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings is not completely known and is a matter of controversy. It is hypothesized that partial depolarization of the cells directly underneath the electrode contributes to the generation of MAP signals. In this paper, we describe a parametric, semi-quantitative method to generate realistic MAP and intermediate forms - multiphasic electrograms different from an ideal MAP - that does not require the partial depolarization hypothesis. The key ideas of our method are the formation of junctional spaces, i.e., electrically isolated pockets between the surface of an electrode and tissue, and the presence of a complex network of passive components that acts as a high-pass filter to distort the signal that reaches the recording amplifier. The passive network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. We show that it is possible to generate different electrograms by the change of the model parameters and that both the MAP and intermediate forms reside on a continuum of signals. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups. SIGNIFICANCERecording the Monophasic Action Potential (MAP) is potentially very useful in both experimental and clinical cardiac electrophysiology and can provide valuable information about the repolarization phase of the action potential. However, despite its benefits, it currently has only a small and niche role. The main challenge is the technical difficulties of recording an ideal MAP. Our results provide a better understanding of the mechanisms of the generation of cardiac electrograms and may help to optimize experiments and improve tools to achieve the full potentials of recording the MAP signals.

biophysics↗