Mechanotransduction is enhanced by the synergistic action of heterotypic cell interactions and TGF-β1.
Mechanotransduction is enhanced by the synergistic action of heterotypic cell interactions and TGF-β1.
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异型细胞相互作用和 TGF-β1 的协同作用增强了机械转导。
DOI：
10.1096/fj.11-199414
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Morgan,JeffreyR
中科院分区：
文献类型：
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作者：
Youssef,Jacquelyn;Chen,Peng;Shenoy,VivekB;Morgan,JeffreyR
随着平面基质和胶原凝胶的使用，机械转导领域已经集中在细胞外基质刚度、机械张力和TGF-β1在产生更具收缩性的成纤维细胞中的作用。然而，很少有人知道细胞间的相互作用在诱导细胞收缩的作用。我们使用三维自组装微组织（其中细胞-细胞相互作用占主导地位）和最近开发的细胞功率测定（机械转导测定）来量化TGF-β1与异型细胞界面对纯正常人成纤维细胞（NHF）和纯大鼠肝细胞35（H35）微组织及其混合物所施加功率的影响。作为对照，我们发现TGF-β1仅使纯NHF和纯H35微组织的功率输出增加一倍，而异型环境导致细胞功率增加5倍（0.24±0.05至1.17±0.13 fJ/h）。将经TGF-β1处理的NHF与未经处理的H35细胞接种证明，异型环境和TGF-β1通过最大化异型细胞相互作用而协同增加细胞功率22倍。使用应力产生的数学模拟，我们表明，张力可以通过异型细胞相互作用来增强。这些数据使人们对异型细胞相互作用如何在伤口愈合过程中增加细胞力产生有了新的认识。Youssef，J.，陈佩，Shenoy，V. B.，摩根，J.R.机械转导通过异型细胞相互作用和TGF-β1的协同作用而增强。
With the use of planar substrates and collagen gels, the field of mechanotransduction has focused on the role of extracellular matrix stiffness, mechanical tension, and TGF-β1 in generating a more contractile fibroblast. However, little is known about the role of cell-cell interactions in inducing cellular contraction. We used 3-dimensional self-assembled microtissues, in which cell-cell interactions dominate, and a recently developed cell power assay (an assay for mechanotransduction) to quantify the effects of TGF-β1 vs. the heterotypic cell interface on the power exerted by pure normal human fibroblast (NHF) and pure rat hepatocyte 35 (H35) microtissues and their mixes. As a control, we found that TGF-β1 only doubled the power output of pure NHF and pure H35 microtissues, whereas the heterotypic environment resulted in a 5-fold increase in cell power (0.24±0.05 to 1.17±0.13 fJ/h). Seeding TGF-β1-treated NHFs with untreated H35 cells demonstrated that the heterotypic environment and TGF-β1 synergistically increase cell power by 22× by maximizing heterotypic cell interactions. Using a mathematical simulation of stress generation, we showed that tensile forces can be enhanced by heterotypic cell interactions. These data render a new understanding of how heterotypic cell interactions may increase cellular force generation during wound healing.—Youssef, J., Chen, P., Shenoy, V. B., Morgan, J. R. Mechanotransduction is enhanced by the synergistic action of heterotypic cell interactions and TGF-β1.