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Mechanotransduction is enhanced by the synergistic action of heterotypic cell interactions and TGF‐β1
Author(s) -
Youssef Jacquelyn,
Chen Peng,
Shenoy Vivek B.,
Morgan Jeffrey R.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-199414
Subject(s) - mechanotransduction , fibroblast , cell , extracellular matrix , microbiology and biotechnology , chemistry , extracellular , cell type , biophysics , cell migration , cell growth , biology , in vitro , biochemistry
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. FASEB J. 26, 2522‐2530 (2012). www.fasebj.org