The effects of artificial E-cadherin matrix-induced embryonic stem cell scattering on paxillin and RhoA activation via alpha-catenin

作者：Mattias Leino; Haque Amranul; Adnan Nihad; Akaike Toshihiro^*

来源：Biomaterials, 2014, 35(6): 1797-1806.

DOI：10.1016/j.biomaterials.2013.11.042

• Embryonic stem cells
• Extracellular matrix
• Cell scattering
• RhoGTPase

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 alpha-catenin revealed that it negatively affects paxillin phosphorylation and upregulates RhoA activity in compact cellular aggregates. Collectively these results indicate that cell scattering might cause a conformational change of alpha-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.

• 出版日期2014-2