UC Santa Barbara

Cell-cell interactions between cardiomyocytes (CMs) are crucial to the structure and function of heart tissue. Due to the force-producing nature of the heart, cell-cell interactions between individual CMs are key to maintaining tissue integrity and mechanotransduction throughout the heart. However, very few studies have focused on CM-CM mechanobiology, and those studies have used murine cells. While animal models are important, they fail to replicate many aspects of human cardiac physiology, including beating rate and contractile protein composition. In this work, I used human induced pluripotent stem cells differentiated into CMs (hiPSC-CMs) to study the role of an adhesive interface mimicking cell-cell adhesion in human CMs. I seeded hiPSC-CMs onto patterns of N-cadherin, a protein critical for cell-cell adhesion in CMs. I used patterns with an elongated shape (7:1 aspect ratio and 1500 µm2 area) to imitate the shape of mature human CMs. I did this patterning both on glass and on a polyacrylamide (PA) hydrogel at a physiologically relevant stiffness (~10 kPa), which imitates the native environment of mature human CMs. hiPSC-CMs adhered to N-cadherin patterns on glass, but not on PA hydrogels. I tested and ruled out several potential causes for the lack of adhesion on gels and propose future work to test other causes.