Jacquelyn Youssef, Peng Chen, Vivek B Shenoy, Jeffrey R Morgan
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2012 JunWith 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.
Jacquelyn Youssef, Peng Chen, Vivek B Shenoy, Jeffrey R Morgan. Mechanotransduction is enhanced by the synergistic action of heterotypic cell interactions and TGF-β1. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2012 Jun;26(6):2522-30
PMID: 22375018
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