Substrate Stiffness Increases Twitch Power of Neonatal Cardiomyocytes in Correlation with Changes in Myofibril Structure and Intracellular Calcium
Substrate Stiffness Increases Twitch Power of Neonatal Cardiomyocytes in Correlation with Changes in Myofibril Structure and Intracellular Calcium
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DOI：
10.1016/j.bpj.2011.09.057
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发表时间：
2011-11-16
影响因子：
3.4
通讯作者：
Sniadecki, Nathan J.
中科院分区：
文献类型：
--
作者：
Rodriguez, Anthony G.;Han, Sangyoon J.;Sniadecki, Nathan J.
在新生儿发育过程中，心肌硬度增加，同时心脏收缩力增加。体外试验表明，基质硬度在调节未成熟心肌细胞产生的抽搐力中起作用。然而，由于难以测量心肌细胞的收缩速度，其对收缩功率的影响尚不清楚。在这里，我们介绍了我们认为是一种新的方法来量化抽搐功率相结合的时间分辨率的光学线扫描的亚细胞力分辨率的微柱阵列。使用这种方法，发现在较硬的柱上培养的细胞的抽搐功率更大，尽管具有较低的抽搐速度。增加的功率部分归因于改善的肌原纤维结构（增加的肌节长度和Z带宽度）和细胞内钙水平。α-肌动蛋白的免疫荧光染色显示，心肌细胞有更大的肌节长度和Z带宽度时，培养在较硬的阵列。此外，细胞内钙的浓度在休息和它的上升与每一个抽搐收缩是更大的细胞在较硬的职位。总之，这些发现表明，心肌细胞响应基板硬度与生物力学和生化变化，导致心脏收缩力的增加。
During neonatal development, there is an increase in myocardial stiffness that coincides with an increase in the contractility of the heart. In vitro assays have shown that substrate stiffness plays a role in regulating the twitch forces produced by immature cardiomyocytes. However, its effect on twitch power is unclear due to difficulties in measuring the twitch velocity of cardiomyocytes. Here, we introduce what we consider a novel approach to quantify twitch power by combining the temporal resolution of optical line scanning with the subcellular force resolution of micropost arrays. Using this approach, twitch power was found to be greater for cells cultured on stiffer posts, despite having lower twitch velocities. The increased power was attributed in part to improved myofibril structure (increased sarcomere length and Z-band width) and intracellular calcium levels. Immunofluorescent staining of a-actin revealed that cardiomyocytes had greater sarcomere length and Z-band width when cultured on stiffer arrays. Moreover, the concentration of intracellular calcium at rest and its rise with each twitch contraction was greater for cells on the stiffer posts. Altogether, these findings indicate that cardiomyocytes respond to substrate stiffness with biomechanical and biochemical changes that lead to an increase in cardiac contractility.