Switch-like Enhancement of Epithelial-mesenchymal Transition by YAP Through Feedback Regulation of WT1 and Rho-family GTPases

The integrity of the expanding epithelial sheets depends on extracellular cues, including cell-cell and cell-matrix interactions. Researchers show that the nano-scale topography of the extracellular matrix underlying epithelial cell layers can strongly affect the speed and morphology of the fronts of the expanding sheet which is dependent on expression of the transcription factor YAP. This process is integral to epithelial to mesenchymal transitions which is a key stage of cancer progression and metastasis.

Originally Published in: Nature Communications (2019) (Link to Paper)

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Superresolution Architecture of Cornerstone Focal Adhesions in Human Pluripotent Stem Cells

This study aims to elucidate the role of cell adhesion to the extracellular matrix plays in maintenance of pluripotency. Researchers used superresolution two-color interferometric photo-activated localization microscopy to examine the three-dimensional architecture of cornerstone adhesions and report vertical lamination of FA proteins. Nanopatterned plates were used to accelerate differentiation of stem cell cultures to help examine the roles of these structural elements.

Originally Published in: Nature Communications (2019) (Link to Paper)

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Matrix Topography Regulates Synaptic Transmission at the Neuromuscular Junction

Recreation of a muscle that can be controlled by the nervous system would provide a major breakthrough for treatments of injury and diseases. However, the underlying basis of how neuron–muscle interfaces are formed is still not understood sufficiently. Here, it is hypothesized that substrate topography regulates neural innervation and synaptic transmission by mediating the cross-talk between neurons and muscles. This hypothesis is examined by differentiating neural stem cells on the myotubes, formed on the substrate with controlled groove width. The substrate with the groove width of 1600 nm, a similar size to the myofibril diameter, serves to produce larger and aligned myotubes than the flat substrate. The myotubes formed on the grooved substrate display increases in the acetylcholine receptor expression. Reciprocally, motor neuron progenitor cells differentiated from neural stem cells innervate the larger and aligned myotubes more actively than randomly oriented myotubes. The results of this study will be broadly useful for improving the quality of engineered muscle used in a series of applications including drug screening, regeneration therapies, and biological machinery assembly.

Originally Published in: Advanced Science (2019) (Link to Paper)

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Microtubule-Actomyosin Mechanical Cooperation During Contact Guidance Sensing

Cancer cell migration through and away from tumors is driven in part by migration along aligned extracellular matrix, a process known as contact guidance (CG). To concurrently study the influence of architectural and mechanical regulators of CG sensing, we developed a set of CG platforms. Using flat and nanotextured substrates with variable architectures and stiffness, we show that CG sensing is regulated by substrate stiffness and define a mechanical role for microtubules and actomyosin-microtubule interactions during CG sensing. Furthermore, we show that Arp2/3-dependent lamellipodia dynamics can compete with aligned protrusions to diminish the CG response and define Arp2/3- and Formins-dependent actin architectures that regulate microtubule-dependent protrusions, which promote the CG response. Thus, our work represents a comprehensive examination of the physical mechanisms influencing CG sensing.

Originally Published in: Cell Reports (2018) (Link to Paper)

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Nanotopography-Induced Structural Anisotropy and Sarcomere Development in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells

Source: Nisa P. Williams, Marcus Rhodehamel, Calysta Yan, Alec S.T. Smith, Alex Jiao, Charles E. Murry, Marta Scatena, Deok-Ho Kim, Engineering anisotropic 3D tubular tissues with flexible thermoresponsive nanofabricated substrates, Biomaterials, Volume 240, 2020, 119856, ISSN 0142-9612.
(Link to Paper)

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