Matrix-guided control of mitochondrial function in cardiac myocytes

Area of Science:

• Biomaterials Science
• Cardiovascular Physiology
• Cellular Metabolism

Background:

• Extracellular matrix (ECM) remodeling accompanies cardiac growth and disease, involving metabolic changes in cardiac myocytes.
• The direct influence of ECM's biochemical and mechanical properties on cardiac myocyte metabolism remains largely unexplored.
• Understanding biomaterial impacts is crucial for developing accurate in vitro models of cardiac tissue.

Purpose of the Study:

• To investigate how ECM biochemical and mechanical properties affect cardiac myocyte morphology and metabolism.
• To compare the responses of neonatal rat ventricular myocytes cultured on different biomaterials.
• To inform the selection of scaffolds for cardiac tissue engineering.

Main Methods:

• Neonatal rat ventricular myocytes were cultured on fibronectin- or gelatin-coated polydimethylsiloxane (PDMS) and gelatin hydrogels with varying elastic moduli.
• Cellular morphology, protein content, and mitochondrial DNA to nuclear DNA ratios were assessed.
• Oxygen consumption rates and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer.

Main Results:

• Cell morphology, protein content, and mitochondrial DNA ratios were maintained across substrates.
• Cytotoxicity was low, with slightly higher levels on PDMS compared to gelatin hydrogels.
• Cardiac myocytes cultured on gelatin hydrogels showed enhanced glycolysis and mitochondrial function (baseline and maximum) compared to those on PDMS substrates, regardless of rigidity.

Conclusions:

• Biochemical cues from the ECM, specifically gelatin, significantly impact cardiac myocyte mitochondrial function.
• Gelatin hydrogels promote better metabolic function in cardiac myocytes than PDMS substrates.
• These findings are vital for understanding matrix regulation of cardiac myocyte physiology and for selecting appropriate biomaterials in cardiac tissue engineering.