The heartbeat: Self-organization of the cardiomyocytes via mechano-chemical feedback

The human heart is a remarkably efficient pump, continuously adapting to meet the body's needs. However, its development—driven by the self-organization of thousands of cells and resulting in nematic order within cardiomyocytes—remains poorly understood. To quantitatively study early heart development, we developed 3D cardiac organoids that closely mimic key aspects of early heart development, such as self-organization of heart-specific cell types, dynamic calcium signaling, and synchronized mechanical contractions. This organoid platform allows for live imaging as well as mechanical and pharmacological perturbations that are not possible in vivo. As the organoids mature, their contractions become increasingly coherent, and contraction frequency rises. This is accompanied by increasing synchrony of calcium activity and alignment of sarcomeres, quantified through a nematic order parameter. Blocking calcium channels halted contractions and reduced nematic order, indicating that cardiomyocytes self-organize through mechanical and chemical feedback loops during maturation. To gain further insight into this phenomenon, we aim to develop a quantitative model that captures the interaction between pulsatile active stress and a remodeling nematic texture representing aligning sarcomeres. These combined experimental and theoretical methods will also enhance our understanding of the complex gene-to-phenotype progression in congenital heart diseases, such as cardiac arrhythmia and Hypertrophic Cardiomyopathy (HCM).