Mechanically Stimulated Contraction of Engineered Cardiac Constructs Using a Microcantilever

The beating heart undergoes cyclic mechanical and electrical activity during systole and diastole. The interaction between mechanical stimulation and propagation of the depolarization wavefront is important for understanding not just normal sinus rhythm, but also mechanically induced cardiac arrhythmia. This study presents a new platform to study mechanoelectrical coupling in a 3-D in vitro model of the myocardium. Cardiomyocytes and cardiac fibroblasts are seeded within extracellular matrix proteins and form constructs constrained by microfabricated tissue gauges that provide in situ measurement of contractile function. The microcantilever of an atomic force microscope is indented into the construct at varying magnitudes and frequencies to cause a coordinated contraction. The results indicate that changes in indentation depth and frequency do not significantly affect the magnitude of contraction, but increasing indentation frequency significantly increases the contractile velocity. Overall, this study demonstrates the validity of this platform as a means to study mechanoelectrical coupling in a 3-D setting, and to investigate the mechanism underlying mechanically stimulated contraction.