Yip AK

Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface

Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated.

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Zyxin Is Involved in Fibroblast Rigidity Sensing and Durotaxis

Focal adhesions (FAs) play an important role in sensing mechanical cues in the extracellular matrix and transducing forces from the extracellular matrix into biological signals (Riveline et al., 2001). The cells can sense and respond to changes in the rigidity of the underlying substrates. When cells are grown on substrates of varying rigidity, they exert larger traction stress and migrate towards more rigid substrates in a phenomenon known as durotaxis (Lo et al., 2000). In order to sense substrate rigidity, the cells apply traction stress through FAs and actin stress fibres to measure mechanical responses of the substrate (Discher et al., 2005; Kobayashi and Sokabe, 2010; Prager-Khoutorsky et al., 2011). While the FA structure of mouse fibroblasts has been elucidated at the nanoscale level (Kanchanawong et al., 2010), little is known about the substrate rigidity sensing mechanisms of the cell.

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Anisotropic traction stresses and focal adhesion polarization mediates topography-induced cell elongation

Cell elongation and differentiation has been shown to be modulated by topographical cues provided by grating substratum. However, little is known about the mechanisms and forces involved in the grating-induced cell elongation, due to the difficulty in fabricating soft elastic gels that allow 3-dimensional (3D) cell traction stress measurements.

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Cell-Cell Adhesion and Cortical Actin Bending Govern Cell Elongation on Negatively Curved Substrates

Physiologically, cells experience and respond to a variety of mechanical stimuli such as rigidity and topography of the extracellular matrix. However, little is known about the effects of substrate curvature on cell behavior. We developed a novel, to our knowledge, method to fabricate cell culture substrates with semicylindrical grooves of negative curvatures (radius of curvature, Rc = 20-100 μm). We found that negative substrate curvatures induced elongation of mesenchymal and epithelial cells along the cylinder axis.

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