Induced coupling between contractile cells

Abstract

Cells communicate with each other through biochemical and electrical mechanisms employing various autocrine and endocrine signaling pathways. Cells, and cardiomyocytes in particular, generate contractile forces on the substrates (or tissues) they adhere to. This results in a tensile strain field in the substrate around the contractile cell. As a result, nearby cells adhered to the same substrate get stretched. The effect of this long range communication has received limited attention to date. Here we develop an elastic cell culture substrate to explore strain mediated coupling in cardiomyocytes. We investigate (1) whether strain coupling of isolated cardiomyocytes affects the temporal dynamics of contractility, (2) whether such long range communication can enable synchrony in cardiomyocyte beating, and (3) what is the biophysical mechanism enabling strain induced coupling? Initial experiments show that strain coupled populations of neonatal rat cardiomyocytes can synchronize their beating with time. We hypothesize that the contraction of one cell cluster results in calcium influx in the coupled cell cluster via stretch sensitive ion channels. We utilize an integrate-and-fire oscillator model with strain induced coupling to predict the emergence of synchrony between cardiomyocytes. This finding may shed light on cardiac arrhythmias in stiffened, infarcted cardiac tissues where strain coupling may be compromised.