Tension development and nuclear eccentricity in topographically controlled cardiac syncytium

The goal of this study was to use topographic control by microfabricated scaffolds with 3-dimensional surfaces to induce active tension development and enhanced contractility in engineered cardiac syncytium (a high density cardiac cell structure with reconstituted cell-to-cell connections and synchronized tissue-like behavior). Deeply microgrooved (feature height 50mum) elastic scaffolds were designed using polydimethylsiloxane molding, and neonatal rat cardiomyocytes were grown on them to confluency. Engineered cardiac cell constructs on the topographically modified (T) scaffolds showed higher order of intra and intercellular organization (fiber-like structures) compared to those grown on various flat surfaces (F), and developed self-organized persisting electrical and mechanical activity. These structural and functional changes were accompanied by a statistically significant (p < 0.001) increase in nuclear eccentricity (mean +/- S.E.: 0.79 +/- 0.01, n = 137 in T vs. 0.64 +/- 0.01, n 863 in F), and a preferential nuclear orientation, deviating from the axis of the grooves at a shallow angle. The orientation of the nuclei correlated well with the actin fiber arrangement in the T-samples, as well as with the direction of maximum displacement. Topography-induced nuclear deformation, a sign of tension development, implies further functional changes in transcription and cell signaling. In conclusion, we demonstrate topographic control of electromechanics in engineered cardiac syncytium, without external mechanical or electrical stimulation. These findings suggest a possibility to use controled microenvironments in the design of biological autonomous force generators with reconstituted excitable tissue.