Speaker
Description
This talk will cover two parts of my research. The first part is on my lab's long-term efforts to use spherical pores as 3D cell cultures. Microwell arrays have emerged as three-dimensional substrates for cell culture due to their simplicity of fabrication and promise for high-throughput applications such as 3D cell-based assays for drug screening. To date, most microwells have had cylindrical geometries. Motivated by our previous findings that cells display 3D physiological characteristics when grown in the spherical micropores of monodisperse foam scaffolds, here we engineered novel spherical microwells. Surprisingly, mesenchymal stem cells in spherical microwells underwent cell cycle arrest, while cells in circular cylindrical microwells of similar diameters proliferate more. Spatial confinement was not sufficient to cause cell-cycle arrest; however, confinement in a constant negative-curvature microenvironment led to cell-cycle arrest. Further transcriptome analysis shows that mesenchymal stem cells are prone to differentitate in spherical microwells, which may be due to chromatin structure changes as evident by morphological changes in nuclei of mesenchymal stem cells in the spherical microwells.
The second part of the talk is on the mechanical wave observed during the wound healing process of zebrafish tailfin. Highly regenerative animals can regrow lost appendages and the rate of regrowth is proportional to the amount of appendage loss. This century-old phenomenon prompted us to investigate whether the mechanism of wound healing, as the first stage of regeneration, is responsible for discerning the amputation position. In vitro studies have revealed great insights into the mechanics of the wound-healing process, including the identification of mechanical waves in collective epithelial cell expansion. It has been suggested that these mechanical waves may also be involved in positional sensing. Here we perform live-cell imaging on adult zebrafish tailfins to monitor the collective migration of basal epithelial cells on tailfin amputation. We observed a cell density wave propagating away from the amputation edge, with the maximum travelling distance proportional to the amputation level and cell proliferation at later stages. We developed a mechanical model to explain this wave behaviour, including the tension-dependent wave speed and amputation-dependent travelling distance. Together, our findings point to an in vivo positional sensing mechanism in regenerative tissues based on a coupling of mechanical signals manifested as a travelling density wave.
