Abstract
Since the discovery of synchronous pulsations in cardiomyocytes (CMs), electrical communication between CMs has been emphasized; however, recent studies suggest the possibility of mechanical communication. Here, we demonstrate that spherical self-beating CM aggregates, termed cardiac spheroids (CSs), produce enhanced mechanical energy under mechanical compression and work cooperatively via mechanical communication. For single CSs between parallel plates, compression increased both beating frequency and beating energy. Contact mechanics revealed a scaling law on the beating energy, indicating that the most intensively stressed cells in the compressed CSs predominantly contributed to the performance of mechanical work against mechanical compression. For pairs of CSs between parallel plates, compression immediately caused synchronous beating with mechanical coupling. Compression tended to strengthen and stabilize the synchronous beating, although some irregularity and temporary arrest were observed. These results suggest that mechanical compression is an indispensable control parameter when evaluating the activities of CMs and their aggregates.
Highlights
Since the discovery of synchronous pulsations in cardiomyocytes (CMs), electrical communication between CMs has been emphasized; recent studies suggest the possibility of mechanical communication
Considering that an isolated CM behaves like a self-excited mechanical oscillator[26], there may exist another mechanism of mechanical communication that achieves the synchronous beating of CMs even with no electrical communication
We describe the mechanical response of human-derived self-beating cardiac spheroids (CSs) (Fig. 1a) observed in two types of tests: (i) compression tests on single CSs and (ii) compression tests on pairs of CSs, where a homemade apparatus (Fig. 1b) was used for both types of tests
Summary
Since the discovery of synchronous pulsations in cardiomyocytes (CMs), electrical communication between CMs has been emphasized; recent studies suggest the possibility of mechanical communication. For pairs of CSs between parallel plates, compression immediately caused synchronous beating with mechanical coupling. Compression tended to strengthen and stabilize the synchronous beating, some irregularity and temporary arrest were observed These results suggest that mechanical compression is an indispensable control parameter when evaluating the activities of CMs and their aggregates. Individual differences inevitably exist between two pendulum clocks, flexible common support may allow their oscillatory motions to interact, keeping their rhythms perfectly matched until one of them stops This fascinating phenomenon, synchronization in coupled oscillators[1], discovered by Christiaan Huygens in 16652, is a universal phenomenon emerging in various fields, such as mechanical2–6, electrical7,8, chemical[9,10], and biological[11,12] systems. The mechanical properties of a single CM have been measured using the deformations of AFM c antilevers[28,29,30], elastic s ubstrates[31,32], and Scientific Reports | (2021) 11:15159
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