Quantitative Evaluation of Cardiac Cell Interactions and Responses to Cyclic Strain

The heart has a dynamic mechanical environment contributed by its unique cellular composition and the resultant complex tissue structure. In pathological heart tissue, both the mechanics and cell composition can change and influence each other. As a result, the interplay between the cell phenotype and mechanical stimulation needs to be considered to understand the biophysical cell interactions and organization in healthy and diseased myocardium. In this work, we hypothesized that the overall tissue organization is controlled by varying densities of cardiomyocytes and fibroblasts in the heart. In order to test this hypothesis, we utilized a combination of mechanical strain, co-cultures of different cell types, and inhibitory drugs that block intercellular junction formation. To accomplish this, an image analysis pipeline was developed to automatically measure cell type-specific organization relative to the stretch direction. The results indicated that cardiac cell type-specific densities influence the overall organization of heart tissue such that it is possible to model healthy and fibrotic heart tissue in vitro. This study provides insight into how to mimic the dynamic mechanical environment of the heart in engineered tissue as well as providing valuable information about the process of cardiac remodeling and repair in diseased hearts.

Automated summary

The unique cellular composition and complex tissue structure of the heart contribute to its dynamic mechanical environment. Changes in both mechanics and cell composition in pathological heart tissue can influence each other, affecting the overall organization of the tissue. The study suggests that varying densities of cardiomyocytes and fibroblasts play a role in controlling tissue organization, allowing for modeling of healthy and fibrotic heart tissue in vitro.