Development of a Nanocomposite-Based Electrochemical Platform for Real-Time Mitochondrial Activity Analysis During Direct Reprogramming into Cardiomyocytes

▲(From left) Professor Tae-Hyung Kim, Dr. Kyeong-Mo Koo (Postdoctoral Fellow), Professor Yoonhee Jin (Yonsei University College of Medicine), and Seungju Seo (Ph.D. Candidate)

- This study provides mechanistic insights into metabolic regulation during cellular reprogramming and holds promise for advancing cardiac regenerative therapeutics.

- A joint research team led by Professor Tae-Hyung Kim at Sungkyunkwan University (SKKU) and Professor Yoonhee Jin at Yonsei University College of Medicine has developed a cutting-edge electrochemical  platform capable of monitoring mitochondrial metabolic activity in real time during the direct reprogramming of cells into cardiomyocyte-like cells (CiCMs). The newly developed platform—a Poly-L-lysine/Matrigel double-layer coated gold nanostructured composite (PMGN)—enables quantitative, nondestructive analysis of mitochondrial function within 30 seconds, offering a powerful tool for tracking metabolic dynamics during cell fate conversion. Cardiovascular diseases remain the leading cause of death globally, and existing treatments largely focus on symptom management rather than restoring damaged heart tissue. While direct reprogramming has emerged as a promising regenerative approach, conventional methods for analyzing cellular function often require fixation or destruction of cells, involve complex procedures, and take hours to complete—limiting their utility in clinical settings. This new platform addresses these challenges by providing a rapid, label-free, and physiologically relevant method for assessing metabolic shifts during reprogramming, potentially paving the way for the development of novel regenerative therapies for cardiac repair.

▲[Figure 1] Schematic Overview of the Nanocomposite-Based Electrochemical Platform for Real-Time Monitoring of Mitochondrial Activity During Direct Cardiac Reprogramming

- To address the limitations of existing analytical methods, the research team engineered a novel functional platform by applying a dual coating of poly-L-lysine and Matrigel onto gold nanostructured electrodes. This design significantly enhances both cell adhesion stability and electrochemical signal sensitivity, enabling reliable and sensitive metabolic measurements. The PMGN is capable of detecting the metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS)—a hallmark of cardiomyocyte reprogramming—within approximately 30 seconds, in real time and without damaging the cells. Notably, the same cells can be repeatedly measured over time, offering a marked improvement in both efficiency and precision compared to conventional assays. Using this system, the team successfully tracked functional metabolic changes in reprogrammed cardiomyocyte-like cells over a long-term culture period of up to 29 days. Furthermore, the platform enabled real-time, label-free, and nondestructive assessment of cardiotoxic responses to four different compounds: doxorubicin, remdesivir, rosiglitazone (known cardiotoxic agents), and liraglutide (a non-toxic control). This achievement demonstrates the system’s potential not only for monitoring cell fate conversion but also for high-throughput cardiotoxicity screening in drug development.

- This research presents broad applicability as a cardiotoxicity prediction platform for cardiovascular drug development, as well as for functional evaluation and quality control of cell-based therapeutics in regenerative medicine. It is expected to serve as a practical turning point in advancing cell therapy and drug development by providing a robust and scalable tool for assessing therapeutic efficacy and safety.

- Keywords: Cell Adhesion Polymers, Gold Nanostructure, Electrochemical Method, Direct Cardiac Reprogramming, Mitochondrial Metabolism, Cardiotoxicity Assessment

- Professor Kim remarked, “The PMGN platform, based on electrochemical mitochondrial activity analysis, enables quantitative assessment of cellular function without causing damage. It is expected to be widely applicable not only for quality control of cardiac regenerative cell therapies, but also for the screening of cardiotoxic drugs and evaluation of their clinical relevance.”He added, “I would like to express my sincere gratitude to SKKU and the Office of Research & Business Foundation for their generous support throughout this research.”

- This research was supported by grants from the Ministry of Science and ICT and the Ministry of Health and Welfare of Korea through the National Research Foundation (NRF), the Regenerative Medicine Technology Development Program, the Korea ARPA-H, and the Korea Health Industry Development Institute (KHIDI). The findings were published on May 30, 2025, in Advanced Composites and Hybrid Materials

(Impact Factor: 23.2), a leading international journal in the field of Materials Science and Composites (top 1.4% in the category).

- Title: In situ monitoring of mitochondrial redox dynamics during cardiac reprogramming using a poly-l-lysine/Matrigel-coated gold nanostructured composite platform