Artificial tissue that mimics the human heart is used to study this organ and its diseases. When immature cardiac cells align into heart-like 3D structures, they behave more like in vivo myocardium than those cultured in 2D.

To investigate why this happens, Simmons et al. investigated how the mechanical tension generated across the 3D tissue formed by aligned cardiomyocytes affects its electrical conduction. . They discovered that sodium channels and gap junctions, two key players in electrical conduction, are turned on in cells under tension, allowing cells to adapt by changing their action potentials.

“Mechanical tension can be used to make induced pluripotent stem cell-derived cardiomyocytes more electrically mature, which can be exploited for disease modeling,” said author Nathaniel Huebsch. .

Arrhythmogenic cardiomyopathy is a genetic disorder associated with mutations in cell-cell junctions that can cause fatal arrhythmias in young athletes. Modeling this disease using induced pluripotent stem cells is difficult because stem cell-derived myocardium is typically immature and even healthy cells exhibit hallmarks of the disease, such as poor conduction and sodium channel dysfunction. It Is difficult.

The authors used mechanical tension to induce features of arrhythmogenic cardiomyopathy in stem cell-derived myocardium. They found that cells with cell-cell junction mutations adapted to increased tension through changes in action potentials, primarily by altering calcium rather than sodium ion influx.

“This may be part of the reason why mutations in cell-cell junctions predispose patients to arrhythmogenic heart disease,” Huebsch said.

Next, the authors want to understand the mechanism by which tension modulates ion channel function. They also plan to study potential treatments for arrhythmogenic heart diseases such as arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy.

sauce: “Altered tissue shape and plakophilin 2 modulate the electrophysiology of human iPS cell-derived cardiomyocytes” Daniel W. Simmons, Ganesh Malayas, David R. Shuftan, Jinxuan Guo, Kasoolelope Oguntuyo, Giska Ramadita, Yuwen Sun, Samuel By D. Jordan, Mary K. Mansell, Brennan Kanderft, Missy Pear, Stacey L. Rentschler, Nathaniel Huebsch, APL bioengineering (2024). This article can be accessed from: https://doi.org/10.1063/5.0160677 .