Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue...

Area of Science:

• Cardiovascular Biology
• Mitochondrial Biology
• Biomaterials Science

Background:

• Mitochondria are vital for cardiac myocyte energy production, with their structure and function changing during development and disease.
• The underlying factors regulating these mitochondrial changes in cardiac myocytes are not well understood.
• Tissue architecture and extracellular matrix (ECM) elasticity also change during cardiac development and disease.

Purpose of the Study:

• To investigate the hypothesis that environmental factors, specifically ECM elasticity and tissue architecture, regulate mitochondrial function in cardiac myocytes.
• To develop a novel method for assessing mitochondrial function in engineered cardiac tissues with controlled environmental parameters.

Main Methods:

• Developed a new technique to embed tunable polydimethylsiloxane (PDMS) disks, microcontact-printed with fibronectin, into cell culture plates.
• Cultured neonatal rat ventricular myocytes on these substrates to form engineered cardiac tissues.
• Measured oxygen consumption rates (OCR) using a Seahorse extracellular flux analyzer to assess mitochondrial function.

Main Results:

• ECM elasticity predominantly regulates basal metabolic parameters in cardiac myocytes.
• Both ECM elasticity and tissue alignment influence the ability of cardiac tissues to adapt to metabolic stress.
• The highest bioenergetic health index was observed in aligned tissues on rigid substrates, indicating optimal mitochondrial function.

Conclusions:

• Mitochondrial function in cardiac myocytes is significantly regulated by both ECM elasticity and myofibril architecture (tissue alignment).
• This study provides new insights into how extracellular cues modulate mitochondrial function in the context of cardiac development and disease.
• The developed methodology allows for independent control and assessment of tissue alignment and matrix elasticity on cellular bioenergetics.