Journal of Sensor Science and Technology (센서학회지)

The Korean Sensors Society (한국센서학회)
권호 표지
DOI QR코드

DOI QR Code

Analysis of the Growth Characteristics of Cardiac Cells According to Mechanical Properties of Substrates Using the Simplified Measurement Technique of Tracker

  • Abdullah, Abdullah (School of Mechanical Engineering, Chonnam National University) ;
  • Kanade, Pooja P. (School of Mechanical Engineering, Chonnam National University) ;
  • Oyunbaatar, Nomin-Erdene (School of Mechanical Engineering, Chonnam National University) ;
  • Jeong, Yun-Jin (School of Mechanical Engineering, Chonnam National University) ;
  • Kim, Dong-Su (School of Mechanical Engineering, Chonnam National University) ;
  • Lee, Dong-Weon (School of Mechanical Engineering, Chonnam National University)
  • Received : 2022.01.19
  • Accepted : 2022.01.27
  • Published : 2022.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

To date, various techniques have been utilized to assess the contractility of cardiomyocytes and their response to drug-induced toxicity. However, these techniques are either invasive or involve complex fabrication methods and expertise. Here, we introduce the use of video-based analysis software to track the motion of cardiomyocytes and assess their contractility. The software, called "Tracker", is freely available and this is the first attempt at using it for cardiac contractility measurement. We used the software to measure the contractile properties of cells cultured on a rigid substrate and two flexible polydimethylsiloxane (PDMS) substrates having different elastic moduli day-wise up to eight days. Contractility was found to be highest in the most flexible substrate. Subsequently, the cardiotoxicity response of the cells on three different substrates was analyzed with verapamil. It was observed that the cells on rigid substrate were primarily affected by drug-induced toxicity, while the drug had a lesser impact on cells on the more flexible PDMS substrate. Evidently, the flexible substrate aided the maturation of cells and had lower drug toxicity, while the cells on PS could not fully mature. The assessment of cardiomyocytes using "Tracker" proved to be simple and reliable.

Keywords

Acknowledgement

This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2017R1E1A1A01074550 and No. 2020R1A5A8018367).

References

  1. E. A. Woodcock and S. J. Matkovich, "Cardiomyocytes structure, function, and associated pathologies", Int. J. Bio-chem. Cell. Biol., Vol. 37, No. 9, pp. 1746-51, 2005. https://doi.org/10.1016/j.biocel.2005.04.011
  2. A. Agarwal, J. A. Goss, A. Cho, M. L. McCain, and K. K. Parker, "Microfluidic heart on a chip for higher throughput pharmacological studies", Lab Chip, Vol. 13, No. 18, pp. 3599-3608, 2013. https://doi.org/10.1039/c3lc50350j
  3. B. Cannon, "Cardiovascular disease: Biochemistry to behavior", Nature, Vol. 493, No. 7434, pp. S2-S3, 2013. https://doi.org/10.1038/493S2a
  4. J. Liu, N. Sun, M. A. Bruce, J. C. Wu, and M. J. Butte, "Atomic force mechanobiology of pluripotent stem cell-derived cardiomyocytes", PloS one, Vol. 7, No. 5, pp. e37559(1)- e37559(7), 2012. https://doi.org/10.1371/journal.pone.0037559
  5. M. L. McCain, H. Yuan, F. S. Pasqualini, P. H. Campbell, and K. K. Parker, "Matrix elasticity regulates the optimal cardiac myocyte shape for contractility", Am. J. Physiol. Heart Circ. Physiol., Vol. 306, No. 11, pp. H1525-H1539, 2014. https://doi.org/10.1152/ajpheart.00799.2013
  6. P. P. Kanade, N. E. Oyunbaatar, and D. W. Lee, "Polymer-based functional cantilevers integrated with interdigitated electrode arrays-A novel platform for cardiac sensing", Micromachines, Vol. 11, No. 4, pp. 450(1)-450(14), 2020. https://doi.org/10.3390/mi11040450
  7. N. E. Oyunbaatar, A. Shanmugasundaram, Y. J. Jeong, B. K. Lee, E. S. Kim, and D. W. Lee, "Micro-patterned SU-8 cantilever integrated with metal electrode for enhanced electromechanical stimulation of cardiac cells", Colloids. Surf. B, Vol. 18, p. 110682, 2020.
  8. J. Kim, W. Han, T. Park, E. J. Kim, I. Bang, H. S. Lee, Y. Jeong, K. Roh, J. Kim, J. S. Kim, C. Kang, C. Seok, J. K. Han, and H. J. Choi, "Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains", Nat. Commun., Vol. 11, No. 1, pp. 1-11, 2020. https://doi.org/10.1038/s41467-019-13993-7
  9. N. E. Oyunbaatar, P. P. Kanade, and D. W. Lee, "Stress-assisted Gold Micro-wrinkles on a Polymer Cantilever for Cardiac Tissue Engineering", Colloids. Surf. B, Vol. 209, p. 112210, 2022. https://doi.org/10.1016/j.colsurfb.2021.112210
  10. J. Schindelin, C. T. Rueden, M. C. Hiner, and K. W. Eliceiri, "The ImageJ ecosystem: An open platform for biomedical image analysis", Mol. Reprod. Dev., Vol. 82, No. 7-8, pp. 518-529, 2015. https://doi.org/10.1002/mrd.22489
  11. J. P. Silva Nunes and A. A. Martins Dias, "ImageJ macros for the user-friendly analysis of soft-agar and wound-healing assays", Biotechniques, Vol. 62, No. 4, pp. 175-179, 2017. https://doi.org/10.2144/000114535
  12. G. Wang, M. L. McCain, L. Yang, A. He, F. S. Pasqualini, A. Agarwal, H. Yuan, D. Jiang, D. Zhang, L. Zangi, J. Geva, A. E. Roberts, Q. Ma, J. Ding, J. Chen, D. Z. Wang, K. Li, J. Wang, R. J. A. Wanders, W. Kulik, F. M. Vaz, M. A. Laflamme, C. E. Murry, K. R. Chien, R. I. Kelley, G. M. Church, K. K. Parker, and W. T. Pu, "Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies", Nat. Med., Vol. 20, No. 6, pp. 616-623, 2014. https://doi.org/10.1038/nm.3545
  13. S. P. Sheehy, F. Pasqualini, A. Grosberg, S. J. Park, Y. Aratyn-Schaus, and K. K. Parker, "Quality metrics for stem cell-derived cardiac myocytes", Stem. Cell. Rep., Vol. 2, No. 3, pp. 282-294, 2014. https://doi.org/10.1016/j.stemcr.2014.01.015
  14. T. Hayakawa, T. Kunihiro, S. Dowaki, H. Uno, E. Matsui, M. Uchida, S. Kobayashi, A. Yasuda, T. Shimizu, and T. Okano, "Noninvasive evaluation of contractile behavior of cardiomyocyte monolayers based on motion vector analysis", Tissue Eng. Part C Methods, Vol. 18, No. 1, pp. 21-32, 2012. https://doi.org/10.1089/ten.tec.2011.0273
  15. A. Ahola, A. L. Kiviaho, K. Larsson, M. Honkanen, K. Aalto Setala, and J. Hyttinen, "Video image-based analysis of single human induced pluripotent stem cell derived cardiomyocyte beating dynamics using digital image correlation", Biomed. Eng. Online, Vol. 13, No. 1, pp. 1-18, 2014. https://doi.org/10.1186/1475-925X-13-1
  16. L. B. Hazeltine, C. S. Simmons, M. R. Salick, X. Lian, M. G. Badur, W. Han, S. M. Delgado, T. Wakatsuki, W. C. Crone, B. L. Pruitt, and S. P. Palecek, "Effects of substrate mechanics on contractility of cardiomyocytes generated from human pluripotent stem cells", Int. J. Cell Biol., Vol. 2012, pp. 508294(1)- 508294(14), 2012. https://doi.org/10.1155/2012/508294
  17. A. J. Ribeiro, Y. S. Ang, J. D. Fu, R. N. Rivas, T. M. Mohamed, G. C. Higgs, D. Srivastava, and B. L. Pruitt, "Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness", PNAS, Vol. 112, No. 41, pp. 12705-12710, 2015. https://doi.org/10.1073/pnas.1508073112
  18. H. L. Waxman, R. J. Myerburg, R. Appel, and R. J. Sung, "Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atrial fibrillation or flutter: a double-blind randomized cross-over study", Ann. Intern. Med., Vol. 94, No. 1, pp. 1-6, 1981. https://doi.org/10.7326/0003-4819-94-1-1
  19. M. P. Aguilar, B. M. Chavez, and R. S. Jauregui, "Using analog instruments in Tracker video-based experiments to understand the phenomena of electricity and magnetism in physics education", Eur. J. Phys., Vol. 39, No. 3, p. 035204, 2018. https://doi.org/10.1088/0143-0807/39/3/035204
  20. L. K. Wee and K. L. Tze, "Video Analysis and Modeling Performance Task to Promote Becoming Like Scientists in Classrooms", Am. J. Educ. Res., Vol. 3, No. 2, pp. 197-207, 2015. https://doi.org/10.12691/education-3-2-13