Summary
Published in American Journal of Physiology-Heart and Circulatory Physiology (2017), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Kofron, C. M., et al. Gq-activated fibroblasts induce cardiomyocyte action potential prolongation and automaticity in a three-dimensional microtissue environment
Gq-activated fibroblasts induce cardiomyocyte action potential prolongation and automaticity in a three-dimensional microtissue environment
Research Overview
Cardiac fibroblasts shape cardiomyocyte behavior in vivo and in 2D culture; this study asked what happens in 3D. Using a scaffold-free platform of interspersed neonatal rat ventricular cardiomyocytes and fibroblasts in nonadhesive hydrogels, Gq-mediated signaling was selectively enhanced in the fibroblasts by adenoviral Gαq infection before co-seeding.
After three days the microtissues were analyzed by signaling assays, histology, qPCR, Western blot, optical mapping with voltage- and calcium-sensitive dyes, and microelectrode recordings of fibroblast resting membrane potential. Enhanced Gq signaling increased microtissue size and profibrotic character, with consequences for cardiomyocyte electrical activity.
Key Discoveries
- Gq signaling selectively enhanced in cardiac fibroblasts within 3D scaffold-free microtissues
- Multi-modal analysis: optical mapping, microelectrode recordings, qPCR, Western blot
- Activated fibroblasts increased microtissue size and profibrotic response, altering cardiomyocyte electrophysiology
