Microtubules regulate cardiomyocyte transversal Young's modulus.

Area of Science:

• Cardiovascular mechanobiology
• Cellular mechanics
• Cardiac physiology

Background:

• Cardiomyocyte mechanobiology is crucial for heart function.
• Titin is a known contributor to cardiomyocyte Young's modulus (YM).
• The role of microtubules (MTs) in cardiac mechanics, especially in myocardial infarction (MI), is understudied.

Purpose of the Study:

• To investigate the contribution of microtubules (MTs) to cardiomyocyte transverse Young's modulus (YM).
• To examine MTs' role in cardiac mechanics under varying mechanical loading and in pathological states like myocardial infarction (MI).
• To understand the impact of MT posttranslational modifications on cardiomyocyte YM.

Main Methods:

• Nanoscale mechanoscanning ion conductance microscopy was employed.
• Cardiomyocytes were analyzed in healthy and pathological states.
• Mechanical loading and unloading conditions were applied.

Main Results:

• MTs significantly contribute to cardiomyocyte transverse YM in both healthy and pathological conditions.
• MT posttranslational modifications differentially affect cardiomyocyte YM: acetylation increases flexibility, while detyrosination increases rigidity.
• No correlation was found between total acetylated and detyrosinated MT protein levels.
• In polymerized MT populations, increased acetylation correlated with decreased detyrosination in an MI model.

Conclusions:

• Microtubules are key regulators of cardiomyocyte mechanical properties.
• Specific MT posttranslational modifications (acetylation and detyrosination) modulate cardiac cell stiffness.
• These findings offer new insights into cardiac mechanics in health and disease, particularly MI.