title: The effects of artificial E-cadherin matrix-induced embryonic stem cell scattering on paxillin and RhoA activation via α-catenin.
abstract: Mechanical forces have been shown to affect stem cell behavior in a large array of ways. However, our understanding of how these mechanical cues may regulate the behavior of embryonic stem cells (ESCs) remains in its infancy. Here, we aim to clarify the effect of cell scattering on the regulation of Rho family GTPases Rac1 and RhoA as well as paxillin. Allowing ESCs to spread and scatter on a synthetically designed E-cadherin substratum causes phosphorylation of paxillin on consensus phosphorylation sites leading to activation of Rac1 and inactivation of RhoA. By culturing cells in presence of RhoA activator or growing cells to a highly confluent state reverses the effect of cell scattering phenotype. Knockdown of E-cadherin-adapter protein α-catenin revealed that it negatively affects paxillin phosphorylation and up-regulates RhoA activity in compact cellular aggregates. Collectively these results indicate that cell scattering might cause a conformational change of α-catenin limiting its capacity to inhibit paxillin phosphorylation that causes an increase in Rac1 activation and RhoA deactivation. Understanding how synthetically designed extracellular matrix affect ESC signaling through mechanical cues brings a new aspect for stem cell engineers to develop technologies for controlling cell function.
authors: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors: Leino
authors: L
authors: Mattias
authors: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan; Department of Biomedical Engineering, University of California, Davis, CA, USA.
authors: Amranul
authors: A
authors: Haque
authors: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors: Nihad
authors: N
authors: Adnan
authors: Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. Electronic address: takaike@bio.titech.ac.jp.
authors: Toshihiro
authors: T
authors: Akaike
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D051379:Mice; D051419:Paxillin / Q000378:metabolism*; D051178:alpha Catenin / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051419:Paxillin; D051178:alpha Catenin; D020742:rhoA GTP-Binding Protein
keywords: Cell scattering; Embryonic stem cells; Extracellular matrix; RhoGTPase