Direct contractility measurement in cardiomyocytes via thin PDMS diaphragm integration with a moving coil actuator: Synergistic maturation through combined topographical and mechanical stimulation

Abstract

Mechanical stimulation within diaphragm-based cell culture platforms presents a promising strategy to enhance cardiomyocyte maturation. However, most of the proposed techniques have met with limited success due to their inability to directly measure the contractile force of cardiomyocytes. This issue primarily stems from the typically thicker diaphragm structure which is necessary to withstand high strain ranges induced by mechanical stimulation. Herein, we propose a moving coil actuator integrated with a thin polydimethylsiloxane (PDMS) diaphragm for precise mechanical stimulation, cell culture, and drug screening applications. This mechanical stimulation system generates desired mechanical deformation to cultured cardiomyocytes without compromising the integrity of the diaphragm structure. The 10 µm thin diaphragm produces significant displacement from the contractility of cultured cardiomyocytes, which can be directly measured using a laser vibrometer system. Cardiomyocytes cultured on nanogroove PDMS diaphragms with and without stimulation and flat diaphragms with stimulation exhibited 4.25-, 2.81-, 2.39-fold enhancements in contraction force and 1.09-, 1.06-, 1.04-, and 1.32-, 1.17-, 1.16-fold enhancements in sarcomere lengths and Connexin 43 (Cx43) compared to counterparts cultured on flat and nanogroove PDMS diaphragms without stimulation. The practicality of the device as a drug screening platform is demonstrated by examining the drug-induced effects on cardiomyocytes using cardiovascular drugs.