Modulation of the contractility of micropatterned myocardial cells with nanoscale forces using atomic force microscopy

Abstract

The ability to modulate cardiomyocyte contractility is important for bioengineering applications ranging from heart disease treatments to biorobotics. In this study, we examined the changes in contraction frequency of neonatal rat cardiomyocytes upon single-cell-level nanoscale mechanical stimulation using atomic force microscopy. To measure the response of same density of cells, they were micropatterned into micropatches of fixed geometry. To examine the effect of the substrate stiffness on the behavior of cells, they were cultured on a stiffer and a softer surface, glass and poly (dimethylsiloxane), respectively. Upon periodic cyclic stimulation of 300 nN at 5 Hz, a significant reduction in the rate of synchronous contraction of the cell patches on poly(dimethylsiloxane) substrates was observed with respect to their spontaneous beat rate, while the cell patches on glass substrates maintained or increased their contraction rate after the stimulation. On the other hand, single cells mostly maintained their contraction rate and could only withstand a lower magnitude of forces compared to micropatterned cell patches. This study reveals that the contraction behavior of cardiomyocytes can be modulated mechanically through cyclic nanomechanical stimulation, and the degree and mode of this modulation depend on the cell connectivity and substrate mechanical properties.