Nuclear morphology and deformation in engineered cardiac myocytes and tissues.
Nuclear morphology and deformation in engineered cardiac myocytes and tissues.
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DOI：
10.1016/j.biomaterials.2010.03.028
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发表时间：
2010-07
期刊：
影响因子：
14
通讯作者：
Parker KK
中科院分区：
文献类型：
--
作者：
Bray MA;Adams WJ;Geisse NA;Feinberg AW;Sheehy SP;Parker KK
心脏组织工程需要对细胞外基质（ECM）微环境进行精细调控，以优化心肌内部结构。心肌细胞核通过细胞骨架成分与细胞膜机械连接，这使其成为细胞对细胞外基质扰动产生反应的靶点。然而，细胞外基质的空间构象以及心肌细胞形状对细胞核位置和形态的作用尚不明确。在本研究中，利用打印的细胞外基质蛋白来构建培养的新生大鼠心室肌细胞的几何形状。采用活细胞荧光成像技术对工程化的一维和二维组织构建体以及单个心肌细胞岛进行检测，以研究在舒张期松弛和收缩期收缩过程中，细胞核位置、形态和运动随所施加的细胞外基质几何形状的变化情况。图像分析表明，在微加工的细胞外基质线条上培养的各向异性组织构建体具有高度的细胞核排列整齐性，类似于在体内的情况；各向同性组织中的细胞核形状多样，且取向明显随机。各向异性组织的细胞核偏心率也有所增加，这表明当细胞在空间上受到限制时，细胞内的力会使细胞核变形。在收缩期，随着组织各向异性的增加，细胞核在位移的大小和方向上受到的空间限制增加，从而产生各向异性变形。因此，收缩期细胞核位移和变形的性质似乎取决于被动的肌原纤维空间组织以及收缩所诱导的主动应力场的共同作用。这些发现对于理解在疾病条件下心肌细胞对其细胞外基质环境的基因影响和功能反应具有重要意义。
Cardiac tissue engineering requires finely-tuned manipulation of the extracellular matrix (ECM) microenvironment to optimize internal myocardial organization. The myocyte nucleus is mechanically connected to the cell membrane via cytoskeletal elements, making it a target for the cellular response to perturbation of the ECM. However, the role of ECM spatial configuration and myocyte shape on nuclear location and morphology is unknown. In this study, printed ECM proteins were used to configure the geometry of cultured neonatal rat ventricular myocytes. Engineered one- and two-dimensional tissue constructs and single-myocyte islands were assayed using live fluorescence imaging to examine nuclear position, morphology and motion as a function of the imposed ECM geometry during diastolic relaxation and systolic contraction. Image analysis showed that anisotropic tissue constructs cultured on microfabricated ECM lines possessed a high degree of nuclear alignment similar to that found in vivo; nuclei in isotropic tissues were polymorphic in shape with an apparently random orientation. Nuclear eccentricity was also increased for the anisotropic tissues, suggesting that intracellular forces deform the nucleus as the cell is spatially confined. During systole, nuclei experienced increasing spatial confinement in magnitude and direction of displacement as tissue anisotropy increased, yielding anisotropic deformation. Thus, the nature of nuclear displacement and deformation during systole appears to rely on a combination of the passive myofibril spatial organization and the active stress fields induced by contraction. Such findings have implications in understanding the genomic consequences and functional response of cardiac myocytes to their ECM surroundings under conditions of disease.
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DOI：
10.1109/34.709565
发表时间：
1998-08-01
影响因子：
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作者：
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DOI：
10.1016/s0304-4165(02)00144-7
发表时间：
2002-02-15
影响因子：
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作者：
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