Figure 1.

Mechanical Coupling Reduces Beating Variability

A representative pair of spontaneously beating cardiac cells 20 μm apart on a flexible substrate. The average frequency is synchronized; however, the right cell is highly stochastic and weakly coupled to the left cell, while the left cell, which is strongly coupled mechanically to the right cell, beats steadily with low variability. This suggests that the left cell (‘slave’) follows the average beating frequency of the right cell (‘master’), whereas its beat-to-beat variability is reduced as a consequence of the strong coupling to the right cell. The left panel (A, C, E, and G) corresponds to the left cell, whereas the right panel (B, D, F, and H) describes the behavior of the right cell. (A) and (B) show the transient frequency vs. time calculated using wavelet analysis; (C) and (D) are the corresponding Fourier transforms (power spectral density [PSD]). (E) and (F) are the strain field generated by the beating cells along the contraction axis (y axis, top) and along the vector connecting to two cells (x axis, bottom). The strain field is shown for a time point where the neighboring cell is relaxed. (G and H), The black curve shows the average strain at the edge of the beating cell along the x axis. The blue and red curves are the normalized beating signals of the left and right cells, respectively, for a short time period where the cells beat in anti-phase (part of the signal shown in I) and are only shown to mark the time position of cell contraction. When the cells beat in anti-phase, we can differentiate between the strain generated by the cell itself and by its neighbor. The strain peaks marked with red dots result from contractions of the right cell, whereas the strain peaks marked with blue dots result from contractions of the left cell. Mechanical coupling for the left cell is calculated as χ_L = |ɛ_xx,R(x = L)/ɛ_xx,L(x = L)|, i.e., by dividing the average strain values generated by the right cell at the edge of the left cell (red dots) by the average strain generated by the left cell next to its edge (blue dots). (I), The blue and red curves are the normalized beating signals of the left and right cells, respectively, for a short time period. Videos showing the fluorescent beads in the underlying substrate (where contractions are apparent) and the calculated strain maps for this time period can be found in the Supplemental Information (Videos S1 and S2).