Matrix elasticity regulates the optimal cardiac myocyte shape for contractility

Area of Science:

• Cardiovascular Biology
• Biophysics
• Cellular Mechanics

Background:

• Concentric hypertrophy involves ventricular thickening and fibrosis, altering myocyte shape.
• The functional impact of reduced myocyte aspect ratio in hypertrophy is not fully understood.
• Reduced myocyte aspect ratio may enhance contractility under stiff extracellular matrix conditions.

Purpose of the Study:

• To investigate how myocyte aspect ratio affects contractility on varying matrix elasticities.
• To determine if reduced myocyte aspect ratio is advantageous in fibrotic conditions.
• To model the contributions of intracellular and extracellular elasticity to cardiac contractility.

Main Methods:

• Neonatal rat ventricular myocytes were engineered into specific aspect ratios on hydrogels of differing stiffness (13 kPa and 90 kPa).
• Cellular contractility and actin/microtubule organization were measured.
• An analytical model was developed to assess intracellular versus extracellular elasticity contributions.

Main Results:

• Myocyte aspect ratio significantly influenced peak systolic work depending on matrix stiffness.
• Lower aspect ratios (∼2:1) maximized work on stiff matrices (90 kPa).
• Model predictions indicated extracellular matrix elasticity plays a dominant role in contractility.

Conclusions:

• Reduced myocyte aspect ratio provides a functional advantage on stiffer extracellular matrices, relevant to cardiac fibrosis.
• The extracellular matrix appears to be a more critical determinant of contractility than intracellular components like microtubules.
• Findings highlight the extracellular matrix as a potential therapeutic target in cardiac disease.