T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.

Area of Science:

• Computational Biology
• Cardiovascular Research
• Biophysics

Background:

• Cardiovascular disease is a leading cause of death globally.
• Existing virtual cardiomyocyte models lack generality and predictive power.
• Improved computational models are needed for mechanistic understanding and therapeutic strategies.

Purpose of the Study:

• Develop a novel, general, and predictive human ventricular cardiomyocyte model.
• Overcome limitations in existing cellular models for arrhythmia research.
• Enhance the translational utility of virtual cardiomyocytes.

Main Methods:

• Developed T-World, a data-driven virtual human cardiomyocyte model.
• Incorporated sex-specific excitation-contraction coupling and signaling pathways.
• Innovated calcium handling mechanisms and ion transporter formulations.

Main Results:

• T-World demonstrates strong agreement with experimental data on electrophysiology and contraction.
• The model accurately predicts drug-induced action potential changes and sympathetic stimulation effects.
• T-World recapitulates key mechanisms of life-threatening arrhythmias and reveals sex-specific differences.

Conclusions:

• T-World is a highly general and predictive open-source model of human ventricular cardiomyocytes.
• The model is suitable for multiscale research on arrhythmogenesis determinants.
• T-World advances computational approaches in cardiovascular research.