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Cells, drugs and safety

Biophysical models of the myocyte, from ion channels to force generation, applied to drug action and safety, to sex hormones, and to carrying results from the laboratory to patients.

The non-genomic and genomic effects of oestrogen on the atrial action potential duration across its concentrations in menopause, the menstrual cycle and pregnancy (A), and representative action potentials at each reproductive phase against baseline, through the non-genomic (C) and the genomic (D) pathway. Panels A, C and D of Figure 2 of Kulkarni et al. (2026), The Journal of Precision Medicine: Health and Disease, in one row, under CC BY 4.0.
The non-genomic and genomic effects of oestrogen on the atrial action potential duration across its concentrations in menopause, the menstrual cycle and pregnancy (A), and representative action potentials at each reproductive phase against baseline, through the non-genomic (C) and the genomic (D) pathway. Panels A, C and D of Figure 2 of Kulkarni et al. (2026), The Journal of Precision Medicine: Health and Disease, in one row, under CC BY 4.0.

At the level of a single myocyte, ionic currents, calcium handling and crossbridge cycling determine the action potential and the force it produces. Models of those processes are used in pharmacological studies of the action potential. Models of the thick filament propose a mechanism for how the force a myocyte produces depends on its length, and are calibrated to measurements from human atrial and ventricular muscle.

Atrial models are used to study how oestrogen alters the risk of atrial fibrillation, and computational models carry the effects of drugs on contraction and relaxation measured in rats over to humans. A model of the human fetal ventricular myocyte at ten weeks of gestation, calibrated to mRNA expression and experimental measurements, describes the ionic currents that govern fetal electrophysiology and calcium handling.

Recent papers

  1. Maximilian Balmus, Sheng‐Ya Wang, Edward W. G. Ashton, Rosie K. Barrows, Molly Monks, Yuzhang Ge, Arthur Lefebvre, Steven A. Niederer, Clinical Pharmacology & Therapeutics, 2026

    In Silico Clinical Trials in Drug Development: Virtual Patients, Applications, and Regulatory Convergence

  2. Cristobal Rodero, Lara Curran, …, Abdul Qayyum, Rosie K. Barrows, Jose A. Solis-Lemus, Shahrokh Rahmani, Marina Strocchi, Angela W.C. Lee, Tiffany M.G. Baptiste, Ludovica Cicci, …, Elias Karabelas, …, Steven A. Niederer, Journal of Molecular and Cellular Cardiology, 2026

    Computational models show that functional remodeling, not anatomy, reshapes physiological determinants of cardiac performance in hypertrophic cardiomyopathy

  3. Aditi Kulkarni, Rosie K. Barrows, Angela W.C. Lee, Caroline H. Roney, Marina Strocchi, Edward J. Vigmond, …, Steven A. Niederer, The Journal of Precision Medicine Health and Disease, 2026

    Multiscale modelling of hormonal effects on atrial fibrillation in female physiology

  4. Alexandre Lewalle, Gregory Milburn, …, Steven A. Niederer, Journal of Molecular and Cellular Cardiology, 2026

    Human atrial skinned muscle fibers exhibit reduced length-dependent activation but show faster force development kinetics than ventricular muscle

  5. Cesare Corrado, Caroline H. Roney, Sanjiv M. Narayan, …, Steven A. Niederer, Communications Medicine, 2025

    The effect of clinically relevant changes in extracellular electrolyte concentrations on human atrial arrhythmias

  6. Aditi Kulkarni, Rosie K. Barrows, Marina Strocchi, Christoph M. Augustin, …, Steven A. Niederer, Functional Imaging and Modeling of the Heart, Lecture Notes in Computer Science, 2025

    Influence of Oestrogen on Atrial Fibrillation Risk: An In-Silico Study

  7. Marina Strocchi, Rosie K. Barrows, Cristobal Rodero, José Alonso Solís-Lemus, Shuang Qian, Ludovica Cicci, Abdul Qayyum, Devran Ugurlu, Christoph M. Augustin, …, Steven A. Niederer, Lecture notes in computer science, 2025

    Multi-scale Whole-Heart Electromechanics Modeling to Link Cellular, Tissue and Systemic Properties to Cardiac Biomarkers in the Diabetic Male and Female Heart

  8. Alexandre Lewalle, Gregory Milburn, …, Steven A. Niederer, Biophysical Journal, 2024

    Cardiac length-dependent activation driven by force-dependent thick-filament dynamics

  9. Marina Strocchi, Stefano Longobardi, Christoph M. Augustin, …, Steven A. Niederer, PLoS Computational Biology, 2023

    Cell to whole organ global sensitivity analysis on a four-chamber heart electromechanics model using Gaussian processes emulators

  10. Alexandre Lewalle, Gregory Milburn, …, Steven A. Niederer, Biophysical Journal, 2023

    Modeling mechanisms of the thick-filament off-state dynamics in cardiac muscle