Drug-induced Changes in Mechanical Behavior of Electrically Synchronized Cardiomyocytes on Surface-patterned Polydimethylsiloxane Diaphragm

Abstract We herein describe the fabrication and evaluation of an electrical stimulator-integrated functional polydimethylsiloxane (PDMS) diaphragm platform to examine the influence of drug toxicity on electrically synchronized cardiomyocytes. The integrated electrical stimulator allows the cardiomyocytes to contract and relax at a specific beat frequency. The growth conditions of the cardiomyocytes can be modulated by controlling the duty cycle, pulse duration, and frequency of the electrical stimulator. Electrical stimulation not only synchronized the beat cycle of the cardiomyocytes but also affected cardiomyocyte maturation. The microgroove structures formed on the PDMS surface had a positive influence on the contractile force through the alignment of the cardiomyocytes. The displacement of the PDMS diaphragm caused by the contractile characteristics of the cardiomyocytes was precisely measured at the nanoscale using a laser displacement sensor. After preliminary experiments were carried out using the platform, two typical cardiovascular drugs (Verapamil and E-4031) were selected to evaluate the performance of the proposed sensor platform. The changes in contraction and beat rate due to drug toxicity were systematically primary in the electrically synchronized and spontaneously beating cardiomyocytes on the PDMS diaphragm. The use of electrically synchronized cardiomyocytes in drug toxicity screening may contribute to elucidating the relationship between mechanical contraction and drugs.