Traction force microscopy of engineered cardiac tissues.
Traction force microscopy of engineered cardiac tissues.
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DOI：
10.1371/journal.pone.0194706
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Parker KK
中科院分区：
文献类型：
--
作者：
Pasqualini FS;Agarwal A;O'Connor BB;Liu Q;Sheehy SP;Parker KK
在体内和体外系统中，心脏组织的发育和病理都被证明敏感地依赖于微环境机械因素，如细胞外基质硬度。我们提出了一种新的定量方法，通过将经典的牵引力显微镜技术扩展到组织水平的准备来评估心脏结构和功能。利用该系统，我们研究了新生大鼠心室肌细胞(NRVM)在模拟软性未成熟心脏微环境(1kPa)、正常心肌微环境(13kpa)和僵硬病变心肌微环境(90kpa)上培养的收缩熟练程度与代谢的关系。我们发现，在最柔软的凝胶上设计的组织产生的压力最小，输出的功也最小。相反，在健康和模拟疾病的凝胶上工程构建的组织中的心肌细胞产生显著更高的应力，在正常硬度的凝胶上工程的NRVM中测得的最大收缩功。有趣的是，尽管软凝胶上的组织表现出较差的压力产生和功产生，但它们的基础代谢呼吸率明显高于其他组，这表明能量产生和收缩功输出之间的耦合非常无效。因此，我们的新平台可以用来定量评估启动组织水平结构和功能重塑的机械转导通路，以响应底物硬度。
Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.
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影响因子：
6.1
作者：
Grosberg A;Alford PW;McCain ML;Parker KK
通讯作者：
Parker KK
DOI：
10.1073/pnas.1304913110
发表时间：
2013-06-11
影响因子：
11.1
作者：
McCain, Megan L.;Sheehy, Sean P.;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
DOI：
10.1073/pnas.1203007109
发表时间：
2012-06-19
影响因子：
11.1
作者：
McCain, Megan L.;Lee, Hyungsuk;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
影响因子：
5.2
作者：
Jacot JG;Kita-Matsuo H;Wei KA;Chen HS;Omens JH;Mercola M;McCulloch AD
通讯作者：
McCulloch AD
影响因子：
4.1
作者：
Baillargeon, Brian;Rebelo, Nuno;Fox, David D.;Taylor, Robert L.;Kuhl, Ellen
通讯作者：
Kuhl, Ellen