Substrate stiffness-modulated registry phase correlations in cardiomyocytes map structural order to coherent beating

Area of Science:

• Biophysics
• Cardiovascular Biology
• Materials Science

Background:

• Substrate stiffness influences muscle fiber structure and function.
• Cardiac muscle cells (cardiomyocytes) exhibit optimized striation and contractile strains with specific substrate rigidities.

Purpose of the Study:

• To theoretically unify the observed dependencies of cardiomyocyte striation and contractile strain on substrate stiffness.
• To develop a model explaining how substrate elasticity affects structural registry and mechanical output.

Main Methods:

• Utilized a statistical physics approach to model elasticity-mediated structural registry as a phase-order parameter.
• Incorporated noise and disorder inherent in biological systems into the theoretical framework.
• Assumed a correlation between structural registration of myofibrils and their in-phase beating.

Main Results:

• Developed a theoretical framework mapping substrate rigidity dependence of registry data onto strain measurements.
• Demonstrated a unified explanation for the observed effects of substrate stiffness on both striation and strain in cardiomyocytes.
• Showed that the elastic environment regulates myofibril structural order.

Conclusions:

• The theoretical model successfully explains experimental observations linking substrate stiffness to cardiomyocyte function.
• Myofibril structural order, influenced by the elastic environment, is a key factor limiting correlated beating in heart cells.
• This work provides a mechanistic understanding of how the biophysical environment impacts cardiac cell mechanics.