Dynamic Myofibrillar Remodeling in Live Cardiomyocytes under Static Stretch

Area of Science:

• Cardiovascular Biology
• Cellular Mechanics
• Microscopy

Background:

• Cardiac hypertrophy, an increase in heart muscle size, occurs due to mechanical load.
• It is critical for understanding heart development and treating heart diseases like those caused by high blood pressure.
• The dynamic process of sarcomeric addition during hypertrophy has not been directly observed.

Purpose of the Study:

• To observe and characterize the dynamic process of sarcomeric addition in cardiomyocytes.
• To investigate the mechanisms of cardiac hypertrophy in real-time.

Main Methods:

• Utilized a custom-built second harmonic generation (SHG) confocal microscope.
• Employed a 3D cell culture system on a deformable substrate under uniaxial stretch.
• Performed live-cell imaging of neonatal cardiomyocytes (CMs).

Main Results:

• Reported the first live-cell observations of dynamic sarcomeric addition.
• Identified three modes of sarcomeric addition: mid-region/end insertion, template-guided sequential addition, and longitudinal splitting.
• Compared real-time observations with static images from hypertrophic hearts.

Conclusions:

• The study provides novel insights into the real-time molecular events driving cardiac hypertrophy.
• The developed 3D culture and SHG imaging techniques are valuable tools for studying hypertrophy models.