Alejandro Carrillo-Meza

Sarcomere Remodeling Under Incremental Stress in Patterned Cardiomyocytes 

Throughout an individual's lifetime, the heart experiences varying levels of stress, such as exercise and disease. At the cellular level, cardiomyocytes, the heart’s muscle cells, adapt to biomechanical stress through dynamic remodeling of myofibrils, muscle fibers composed of sarcomeres assembled by Z-discs. Currently, the underlying mechanisms behind sarcomere remodeling are not well known. This presentation explores efforts to promote sarcomere remodeling in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) through stretching experiments. We stretched hiPSC-CMs with 15% incremental strain along their short and long axes. Sarcomere structures were captured before stretching, at 15, and at 60 minutes on a single-cell pattern polydimethylsiloxane (PDMS) substrate. We aim to quantify Z-disc band length and number using engineered cell lines with alpha-actinin tagged with green fluorescent protein (GFP) and analyze the data with Fiji Labkit. We expect preliminary results to show noticeable increases in the Z-band length (more Z-disc addition in parallel) with both horizontal and vertical stretching at 15 and 60 minutes. These results would indicate that sarcomere remodeling is differentially regulated by the direction of mechanical stretching, suggesting a complex interplay between biomechanical stress directionality and sarcomere dynamics. If successful, such findings may offer potential avenues for developing novel models for cardiac diseases and coupling stretching with contractile modulator treatments.