Stretch Harmonizes Sarcomere Strain Across the Cardiomyocyte

Area of Science:

• Cardiovascular Physiology
• Muscle Biology
• Cellular Mechanics

Background:

• The Frank-Starling mechanism describes increased cardiomyocyte contraction with myocardial stretch.
• The precise sarcomere-level mechanisms driving this phenomenon remain incompletely understood.
• Investigating intersarcomere dynamics during cell lengthening is crucial.

Purpose of the Study:

• To elucidate how sarcomere contractile synchrony and intersarcomere dynamics enhance cardiomyocyte contractility during stretch.
• To determine the role of titin in regulating these dynamics.

Main Methods:

• Simultaneous recording of sarcomere strain and intracellular calcium (Ca2+) in isolated cardiomyocytes.
• Experiments conducted at resting length and following stepwise cell lengthening.
• Utilized rat and titin-haploinsufficient mouse models.

Main Results:

• Unstretched cardiomyocytes exhibit nonuniform sarcomere deformation, with some sarcomeres stretching or remaining stationary.
• Cell lengthening recruits additional shortening sarcomeres, improving contractile efficiency.
• Titin haploinsufficiency leads to increased sarcomere length variability, reduced recruitment of shortening sarcomeres, and impaired contractility.

Conclusions:

• Sarcomere recruitment and strain harmonization are key to increased contractility during cell stretch.
• Titin plays a critical role in setting sarcomere dimensions and controlling sarcomere recruitment.
• Reduced titin expression impairs cardiomyocyte contractility through altered intersarcomere dynamics.