Carbon nanotubes enhance intercalated disc assembly in cardiac myocytes via the β1-integrin-mediated signaling pathway.
Carbon nanotubes (CNTs) offer a new paradigm for constructing functional cardiac patches and repairing myocardial infarction (MI). However, little is known about how CNTs enhance the mechanical integrity and electrophysiological function of cardiac myocytes. To address this issue, we investigated the regularity and precise mechanism of the influence of CNTs on the assembly of intercalated disc (IDs). Here, single walled CNTs incorporated into collagen substrates were utilized as growth supports for neonatal cardiomyocytes, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, western blotting, transmission electron microscopy, and intracellular calcium transient measurement, we discovered that the addition of CNTs remarkably increased ID-related protein expression and enhanced ID assembly and functionality. On that basis, we further explored the underlying mechanism for how CNTs enhanced ID assembly through the use of immunohistochemical staining and western blotting. We found that the β1-integrin-mediated signaling pathway mediated CNT-induced upregulation of electrical and mechanical junction proteins. Notably, CNTs remarkably accelerated gap junction formation via activation of the β1-integrin-mediated FAK/ERK/GATA4 pathway. These findings provide valuable insight into the mechanistic effects that CNTs have on neonatal cardiomyocyte performance and will have a significant impact on the future of nanomedical research.
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China; Chengdu Military General Hospital, Chengdu, Sichuan Province 610083, PR China.
Hongyu
H
Sun
Affiliated Hospital of Academy of Military Medical Sciences, Beijing, PR China.
Shuanghong
S
Lü
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China.
Xiao-Xia
XX
Jiang
Affiliated Hospital of Academy of Military Medical Sciences, Beijing, PR China.
Xia
X
Li
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China.
Hong
H
Li
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China.
Qiuxia
Q
Lin
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China.
Yongchao
Y
Mou
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China.
Yuwei
Y
Zhao
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China.
Yao
Y
Han
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China. Electronic address: sisun819@yahoo.com.
Jin
J
Zhou
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, 27 Taiping Rd, Beijing 100850, PR China. Electronic address: wcy2000_te@yahoo.com.
Changyong
C
Wang
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000737:chemistry; D002448:Cell Adhesion; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry; D018031:Connexin 43 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017629:Gap Junctions; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D050997:Nanomedicine / Q000379:methods; D037742:Nanotubes, Carbon / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013314:Stress, Mechanical; D054457:Tissue Scaffolds / Q000737:chemistry
D018031:Connexin 43; C580592:Gja1 protein, rat; D019012:Integrin beta1; D037742:Nanotubes, Carbon; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium
Carbon nanotubes; Collagen; ERK; Intercalated disc; Neonatal cardiomyocytes; β1-integrin