Changes in cardiac myocyte shape alter transcriptional expression of cell‐to‐cell junction proteins

The main objective of this study was to determine whether changes in shape of neonatal rat cardiac myocytes (NVRM) and substrate stiffness alter the expression of receptor proteins associated with cell‐ to‐cell and cell‐to‐extracellular matrix (ECM) adhesions. Confluent monolayers of NVRM were cultured on anisotropic/isotropic substrates of varying stiffness. Anisotropic substrates were micropatterned with 5μm wide fibronectin lines whereas isotropic substrates were uniformly coated with fibronectin. NVRM on anisotropic patterns exhibited an elongated and spindle‐like shape whereas those on isotropic substrates randomly spread in all directions. qRT‐PCR analysis demonstrated that when anisotropy was imposed, cardiac myocytes exhibited significantly higher transcriptional levels of cell‐to‐cell adhesion molecule N‐cadherin and gap junction associated molecule connexin‐43 than the isotropic cells (Fig 1). However, the mRNA level of integrin‐β1, which binds to ECM matrix, was altered only moderately in response to the imposed anisotropy. Increasing substrate stiffness reduced integrin‐β1 mRNA levels and moderately increased the N‐cadherin and connexin‐43 levels. This study suggests that changes in myocyte shape mainly affect cell‐to‐cell mediated adhesions implicating that they are critical determinants of cardiac mechanotransduction. Grant Funding Source : NIH, PA Department of Health