Mechanobiology in vivo and in 3D

This talk will cover two parts of my research. The first part is to solve the century-old mystery on how highly regenerative animals can regrow lost appendages with the rate proportional to the amount of tissue lost. We investigated what mechanism of wound healing, as the first stage of regeneration, is responsible for discerning the amputation position. 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.
 
The second part of the talk will be 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 microwells shaped as spherical caps with obtuse polar angles, yielding narrow apertures. We found distinct cell behaviors between epithelial cells and fibroblast cells when cultured in spherical microwells. Epithelial cells proliferate and maintain their polarity based on the extracellular matrix coating; while mesenchymal cells stop proliferating in small spherical microwells. These two types of cells also opposite curvotaxis trends. In short, these investigations demonstrate that spherical microwells open up new directions to explore mechanobiology.