A novel perspective on the regulation of cardiac cell beating: cardiac cell under mechanical stimulation acts as “cell activation button” to activate adjacent cardiac cell

Figures

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  Fig. 1. The micro-manipulation platform for mechanical stimulation of cardiac cells. The whole experiment is performed on this platform. (a) and (b) are the physical diagram and schematic diagram of the micro-manipulation platform respectively. The platform mainly consists of an inverted microscope with an X-Y electric stage, a micromanipulator and a camera. Through the real-time feedback captured by the camera, the stage is controlled to move cardiac cells to the target position, and the 3-degree-of-freedom micromanipulator loaded with a mechanical probe is controlled to apply the mechanical stimulation of the cardiac cells

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  Fig. 2. The mechanical probe can act as an external activation device for cardiac cells. (a) Schematic and (b) experimental image of mechanical stimulation using a mechanical probe. (c) Average displacement of the cell contour under stimulation: blue curve (quiescent state) and red curve (activated state). (d) Three mechanical response phenotypes observed in quiescent cells. (e) Percentage distribution of response phenotypes (n = 30 cells; 22 activated, 8 non-activated). Chi-square test confirms statistical significance (*P < 0.05). Scale bar: 30-µm

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  Fig. 3. Mechanically activated cardiac cell can act as “cell activation button” to activate adjacent cell. (a) and (b) show the schematic diagram and optical experimental image of the “cell activates cell” mode under mechanical stimulation. (c) Response curves of the activation cell(blue) and the target cell(red). (d) The activation cell is mechanically stimulated at 1.37 s, activating the target cell within < 0.1 s. (e) Percentage distribution of activated target cells(n = 21 cells; 16 activated, 5 non-activated). Chi-square test confirms statistical significance (*P < 0.05). Scale bar: 30-µm

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  Fig. 4. Calcium imaging reveals the bioelectrical signal conduction mechanism. (a-b) Spontaneous calcium transients in unstimulated cells, showing hierarchical signaling from a “dominant cell” to adjacent cells. (c-d) Mechanical stimulation induces calcium influx in the activation cell, which propagates to the target cell via intercellular junctions. Scale bar: 30-µm