Dilated cardiomyopathies are genetic diseases characterized by defects in the mechanical and electrical activity of the heart tissue. Some of these cardiomyopathies are caused by a mutation in the DES gene, which encodes desmin, a crucial intermediate filament for the maintenance of the structure of muscle cells. Many cell-based studies have shown how desmin mutations can affect the contractility of cardiomyocytes, but little is still known about the role of desmin in controlling the organization, mechanical and electrical functionality of the heart tissue.

In this study we want to evaluate the effect of mutations of desmin on the contractility of cardiac micro-tissues.

After derivation of cardiomyocytes derived from human induced pluripotent stem cell (hiPSC-CMs) from hiPSCs using a cardiac differentiation protocol, a 3D co-culture model called a “spheroid” was established by self-aggregation of different cardiac cell types. A custom Matlab framework is being developed to analyze movies of spheroid contractions using a Kanade–Lucas–Tomasi (KLT) feature tracker. Ten strains of spheroids, both with and without mutations in the DES gene will be compared by analyzing their contraction kinetics and their deformation during the contractions.

The framework detects ROIs (regions of interest) and measures their displacement during the movies. It can then use the frequency decomposition of the displacement signals to filter out the ROIs for which a movement is not detected. This filtering greatly improves the detection of the spheroid contractions and measurement of the contraction parameters. The automaticanalysis of spheroid contraction films allows for a high-throughput measurement of contraction parameters, which can be used to train machine-learning models. These show that some mutations of desmin tend to decrease the speed at which the spheroids contract. The analysis of the ROI beatings reveals structural defects in the spheroids.

The analytical framework presented here highlights the contributions of different regions of the spheroid to the contraction of the whole tissue. Analysis are being run on different cardiomyocyte strains to assess the effect of desmin mutations on the beatings of the cardiomyocytes.