Mechanical communication through the ECM is frequency-dependent due to cell sensitivity to mechanical signal shape

Cells communicate mechanically by sensing and responding to mechanical deformations generated by their neighbors in the extracellular matrix (ECM). By directly measuring the mechanical coupling between a cardiac cell and an artificial mechanical cell and monitoring the dependence of beat-to-beat variability on mechanical coupling, we can quantify the sensitivity of cardiac cells to mechanical signals. Here we show that due to the dynamic viscoelastic properties of collagen hydrogels (a major component of the cardiac ECM), the shape of the mechanical signal changes in a frequency-dependent manner as it propagates through the gel, resulting in mechanical communication that depends on beating frequency. Moreover, we show that cardiac cell sensitivity to the shape of the mechanical signal results from its responsiveness to the loading rate, with an optimal loading rate for efficient mechanical communication. The dependence of signal shape on ECM viscoelasticity and the existence of an optimal loading rate suggest that there are ideal viscoelastic properties for mechanical communication between cardiac cells.