Sarcomere alignment is regulated by myocyte shape
Sarcomere alignment is regulated by myocyte shape
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DOI：
10.1002/cm.20290
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发表时间：
2008-08-01
影响因子：
--
通讯作者：
Parker, Kevin Kit
中科院分区：
文献类型：
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作者：
Bray, Mark-Anthony;Sheehy, Sean P.;Parker, Kevin Kit
心脏器官发生和发病机制都以心肌细胞形态、细胞骨架结构和细胞外基质(ECM)的变化为特征。然而，ECM影响心肌细胞形态和肌原纤维构型的机制尚不清楚。我们假设ECM中的几何线索通过引导肌动蛋白网络方向来对齐肌节。为了验证我们的假设，我们将新生大鼠的心室肌细胞培养在微图案化的细胞外基质岛上，以测量它们如何重塑细胞骨架以响应细胞外提示。根据细胞外基质的边界条件，心肌细胞呈圆形和矩形岛状扩散，并重组其细胞骨架和肌原纤维阵列。环状肌细胞既不组装可预测的肌动蛋白网络，也不组织肌节阵列。相反，在长宽比从1：1到7：1的矩形ECM模式下培养的心肌细胞，基于高度定位的焦点黏附复合体，以可预测和可重复的模式排列肌节。对平均α-肌动蛋白图像的检查显示，肌小节登记不变，与肌细胞纵横比无关。由于肌节亚单位具有固定的长度，这一观察表明细胞骨架的构型受细胞外边界条件的长度限制。这些结果表明，细胞外微环境的改变会导致心肌细胞形态和细胞内结构的动态重构。此外，几何边界，如角，会引起局部的肌原纤维各向异性，这种各向异性随着肌细胞纵横比的增加而变得全局性。
Cardiac organogenesis and pathogenesis are both characterized by changes in myocyte shape, cytoskeletal architecture, and the extracellular matrix (ECM). However, the mechanisms by which the ECM influences myocyte shape and myofibrillar patterning are unknown. We hypothesized that geometric cues in the ECM align sarcomeres by directing the actin network orientation. To test our hypothesis, we cultured neonatal rat ventricular myocytes on islands of micropatterned ECM to measure how they remodeled their cytoskeleton in response to extracellular cues. Myocytes spread and assumed the shape of circular and rectangular islands and reorganized their cytoskeletons and myofibrillar arrays with respect to the ECM boundary conditions. Circular myocytes did not assemble predictable actin networks nor organized sarcomere arrays. In contrast, myocytes cultured on rectangular ECM patterns with aspect ratios ranging from 1:1 to 7:1 aligned their sarcomeres in predictable and repeatable patterns based on highly localized focal adhesion complexes. Examination of averaged alpha-actinin images revealed invariant sarcomeric registration irrespective of myocyte aspect ratio. Since the sarcomere sub-units possess a fixed length, this observation indicates that cytoskeleton configuration is length-limited by the extracellular boundary conditions. These results indicate that modification of the extracellular microenvironment induces dynamic reconfiguring of the myocyte shape and intracellular architecture. Furthermore, geometric boundaries such as corners induce localized myofibrillar anisotropy that becomes global as the myocyte aspect ratio increases.