Event Title : Discovery of longitudinal myofiber system in heart ventricular walls

Session Theme : Macromolecular structure and function, Session Chair : Vinothkumar KR
Speaker Name: 
Drisya Dileep
Start Time: 
Wednesday, January 12, 2022 - 17:35
End Time: 
Wednesday, January 12, 2022 - 17:45
Talks Abstract: 

Heart is made of specialized muscle cells called cardiomyocytes, which contains an array of subcellular structures sarcomere. These sarcomeres contract in coordinated fashion to generate a unidirectional wringing motion, essential for effective blood pumping throughout an organism. From its shape and electrical propagation patterns, researchers have speculated that the cardiomyocytes are organized as contractile fibers (myofibers) across heart walls. Further, several models converge to suggest that these myofibers are arranged in a helicoid fashion across different regions of heart. These models are derived from low-resolution diffusion-tensor imaging and modeling, it is still not clear how the cardiomyocytes are organized at cellular level and whether there is a helical arrangement of muscle fibers in heart. Here we report the first reconstruction of myocyte geometry across the entire ventricular wall of mouse heart, at micron scale. We achieve this by clearing the mouse heart and the entire short axis and long axis sections stained with cell membrane specific fluorescent dyes were subjected to light microscopy based deep imaging. We then apply computer vision methods to estimate the cell orientation from the composite image stacks of the whole area of heart tissue section. Thus, the imaging and computational analysis yields ~ 3 order magnitude gain in resolution compared to the existing models that describe myofiber organization of heart ventricles. Our reconstructions at the cellular scale in intact tissue reveal entirely new features of the structural arrangement of cardiomyocytes, including, sharp transitions of cell/myofiber orientations and an array of myofibers orthogonal to the myocardium (or circumferential fibers). Combinedly from our data, we hypothesize that the intertwined orthogonal fiber system is important for coordinating contraction, electrical wave propagation and the opening-closing cycle of atrioventricular valves.  Our work provides organizational principles that will be invaluable for understanding the 3D architecture that make up heart tissue and their dysfunction during cardiomyopathy disease progression.

Event Day: 
Day 3 (12th Jan 2022)