Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture.
Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture.
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DOI：
10.1016/j.biomaterials.2012.04.043
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发表时间：
2012-08
期刊：
影响因子：
14
通讯作者：
Parker, Kevin Kit
中科院分区：
文献类型：
--
作者：
Feinberg, Adam W.;Alford, Patrick W.;Jin, Hongwei;Ripplinger, Crystal M.;Werdich, Andreas A.;Sheehy, Sean P.;Grosberg, Anna;Parker, Kevin Kit
心脏是一个具有包裹层的肌肉器官，其层状结构中嵌入了神经网络、血管网络、胶原纤维、成纤维细胞和心肌细胞，这些结构有助于心脏收缩。我们假设这些非肌肉成分可能具有功能上的益处，在心肌细胞的细胞间和细胞内组织中作为重要的结构排列线索。先前的研究已经表明，工程化心肌的排列可增强钙处理能力，但这如何影响实际的力产生仍不清楚。需要定量分析来确定排列对收缩功能和肌肉生理学的影响。为了测试这一点，我们使用微图案化表面从新生大鼠心室肌细胞构建具有不同结构的二维心肌：融合的各向同性（作为未排列的对照）、融合的各向异性以及间隔20μm的平行多细胞心肌纤维阵列。我们将肌节取向的图像分析与肌肉薄膜收缩力测定相结合，以便计算作为组织结构函数的肌节产生的峰值应力。在此我们报告，工程化心脏组织中收缩期峰值应力的增加与肌节排列的增加相对应。这种变化比仅由增强的钙处理和单轴排列增加所预期的要大。这些结果表明，细胞外空间中编码的边界条件（异质性）可以调节肌肉组织的功能，并且结构组织和细胞骨架排列对于最大化峰值力的产生至关重要。
The heart is a muscular organ with a wrapping, laminar structure embedded with neural and vascular networks, collagen fibrils, fibroblasts, and cardiac myocytes that facilitate contraction. We hypothesized that these non-muscle components may have functional benefit, serving as important structural alignment cues in inter- and intra-cellular organization of cardiac myocytes. Previous studies have demonstrated that alignment of engineered myocardium enhances calcium handling, but how this impacts actual force generation remains unclear. Quantitative assays are needed to determine the effect of alignment on contractile function and muscle physiology. To test this, micropatterned surfaces were used to build 2-dimensional myocardium from neonatal rat ventricular myocytes with distinct architectures: confluent isotropic (serving as the unaligned control), confluent anisotropic, and 20 μm spaced, parallel arrays of multicellular myocardial fibers. We combined image analysis of sarcomere orientation with muscular thin film contractile force assays in order to calculate the peak sarcomere-generated stress as a function of tissue architecture. Here we report that increasing peak systolic stress in engineered cardiac tissues corresponds with increasing sarcomere alignment. This change is larger than would be anticipated from enhanced calcium handling and increased uniaxial alignment alone. These results suggest that boundary conditions (heterogeneities) encoded in the extracellular space can regulate muscle tissue function, and that structural organization and cytoskeletal alignment are critically important for maximizing peak force generation.
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影响因子：
--
作者：
Bray, Mark-Anthony;Sheehy, Sean P.;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
DOI：
10.1126/science.1177350
发表时间：
2009-10-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Domian IJ;Chiravuri M;van der Meer P;Feinberg AW;Shi X;Shao Y;Wu SM;Parker KK;Chien KR
通讯作者：
Chien KR
DOI：
10.1109/34.709565
发表时间：
1998-08-01
影响因子：
23.6
作者：
Hong, L;Wan, YF;Jain, A
通讯作者：
Jain, A
影响因子：
2.7
作者：
Nalivaiko, Eugene;Antunes, Vagner R.;Paton, Julian F. R.
通讯作者：
Paton, Julian F. R.
影响因子：
5.5
作者：
Fedorov, Vadim V.;Lozinsky, Ilya T.;Efimov, Igor R.
通讯作者：
Efimov, Igor R.