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Engineering micromyocardium to delineate cellular and extracellular regulation of myocardial tissue contractility
Integrative Biology ( IF 1.5 ) Pub Date : 2017-07-12 00:00:00 , DOI: 10.1039/c7ib00081b Nethika R. Ariyasinghe 1, 2, 3, 4, 5 , Caitlin H. Reck 1, 2, 3, 4, 5 , Alyssa A. Viscio 1, 2, 3, 4, 5 , Andrew P. Petersen 1, 2, 3, 4, 5 , Davi M. Lyra-Leite 1, 2, 3, 4, 5 , Nathan Cho 1, 2, 3, 4, 5 , Megan L. McCain 1, 2, 3, 4, 5
Integrative Biology ( IF 1.5 ) Pub Date : 2017-07-12 00:00:00 , DOI: 10.1039/c7ib00081b Nethika R. Ariyasinghe 1, 2, 3, 4, 5 , Caitlin H. Reck 1, 2, 3, 4, 5 , Alyssa A. Viscio 1, 2, 3, 4, 5 , Andrew P. Petersen 1, 2, 3, 4, 5 , Davi M. Lyra-Leite 1, 2, 3, 4, 5 , Nathan Cho 1, 2, 3, 4, 5 , Megan L. McCain 1, 2, 3, 4, 5
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Cardiovascular diseases are a leading cause of death, in part due to limitations of existing models of the myocardium. Myocardium consists of aligned, contractile cardiac myocytes interspersed with fibroblasts that synthesize extracellular matrix (ECM). The cellular demographics and biochemical and mechanical properties of the ECM remodel in many different cardiac diseases. However, the impact of diverse cellular and extracellular remodeling on the contractile output of the myocardium are poorly understood. To address this, we micropatterned 13 kPa and 90 kPa polyacrylamide gels with aligned squares of fibronectin (FN) or laminin (LN). We seeded gels with two concentrations of primary neonatal rat ventricular myocytes, which naturally contain fibroblasts. Cells assembled into aligned “μMyocardia” with fibroblast
:myocyte ratios dependent on initial seeding concentration. Using traction force microscopy (TFM), we found that the peak systolic longitudinal cross-sectional force was similar across conditions, but the peak systolic work was significantly lower on 90 kPa gels. This indicates that ECM elasticity dominates over ECM ligand and cell demographics in regulating contractile output. Because our platform provides independent control over cell–cell and cell–matrix interactions, it has many applications for cardiac disease modeling.
中文翻译：
工程微心肌，描绘心肌组织收缩的细胞和细胞外调节
心血管疾病是导致死亡的主要原因，部分原因是现有心肌模型的局限性。心肌由排列成排的，收缩的心肌细胞和散布在纤维中的合成细胞外基质（ECM）组成。在许多不同的心脏病中，ECM的细胞人口统计学特征以及生化和力学性质都会发生变化。但是，人们对各种各样的细胞和细胞外重塑对心肌收缩输出的影响知之甚少。为了解决这个问题，我们用纤连蛋白（FN）或层粘连蛋白（LN）的对齐方格微图案化了13 kPa和90 kPa聚丙烯酰胺凝胶。我们用两种浓度的天然新生大鼠心室肌细胞（天然含有成纤维细胞）接种了凝胶。细胞与成纤维细胞组装成对齐的“μ心肌”：肌细胞比例取决于初始接种浓度。使用牵引力显微镜（TFM），我们发现整个条件下的收缩期纵向纵截面力峰值相似，但在90 kPa凝胶上，收缩期峰值功明显更低。这表明在调节收缩输出中，ECM弹性比ECM配体和细胞人口统计学更为重要。由于我们的平台可独立控制细胞-细胞和细胞-基质的相互作用，因此在心脏病建模中具有许多应用。
更新日期：2017-09-18
:myocyte ratios dependent on initial seeding concentration. Using traction force microscopy (TFM), we found that the peak systolic longitudinal cross-sectional force was similar across conditions, but the peak systolic work was significantly lower on 90 kPa gels. This indicates that ECM elasticity dominates over ECM ligand and cell demographics in regulating contractile output. Because our platform provides independent control over cell–cell and cell–matrix interactions, it has many applications for cardiac disease modeling.
中文翻译：
工程微心肌，描绘心肌组织收缩的细胞和细胞外调节
心血管疾病是导致死亡的主要原因，部分原因是现有心肌模型的局限性。心肌由排列成排的，收缩的心肌细胞和散布在纤维中的合成细胞外基质（ECM）组成。在许多不同的心脏病中，ECM的细胞人口统计学特征以及生化和力学性质都会发生变化。但是，人们对各种各样的细胞和细胞外重塑对心肌收缩输出的影响知之甚少。为了解决这个问题，我们用纤连蛋白（FN）或层粘连蛋白（LN）的对齐方格微图案化了13 kPa和90 kPa聚丙烯酰胺凝胶。我们用两种浓度的天然新生大鼠心室肌细胞（天然含有成纤维细胞）接种了凝胶。细胞与成纤维细胞组装成对齐的“μ心肌”
：肌细胞比例取决于初始接种浓度。使用牵引力显微镜（TFM），我们发现整个条件下的收缩期纵向纵截面力峰值相似，但在90 kPa凝胶上，收缩期峰值功明显更低。这表明在调节收缩输出中，ECM弹性比ECM配体和细胞人口统计学更为重要。由于我们的平台可独立控制细胞-细胞和细胞-基质的相互作用，因此在心脏病建模中具有许多应用。
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