Keng-Hui Lin

Physics as a cellular signal for biological functions

Abstract: 

This talk will cover two parts of my research. The first part is on the mechanical wave observed in the wound healing 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.
 
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. When used as bare substrates, these microwells were suitable for culturing cell spheroids; the narrow apertures sterically hindered unattached cultured cells from rolling out of microwells under agitation. When only the walls of the microwell were conjugated with extracellular matrix proteins, cells remained confined in the microwells. Epithelial cells proliferated and burst out of the aperture, and cell polarity was oriented based on the distribution of extracellular matrix proteins in the microwells. Surprisingly, single fibroblast cells in spherical wells of various diameters (40–100 μm) underwent cell cycle arrest, while cells in circular cylindrical microwells continued to proliferate. Spatial confinement was not sufficient to cause cell-cycle arrest; however, confinement in a constant negative-curvature microenvironment led to cell-cycle arrest. Overall, these investigations demonstrate that cells in the spherical microwells exhibit different behaviors from their 2D counterparts. 

Speaker: Keng-Hui Lin, Academia Sinica (Taiwan)

Keng-hui Lin is currently a research fellow at Institute of Physics, Academia Sinica (AS), Taipei, Taiwan. She earned her B.Sc. in physics from National Taiwan University and her Ph.D. in Physics from University of Pennsylvania, where she specialized in experimental soft matter physics. She carried out her postdoctoral work on the nanowire-based biosensors at Dept. of Chemistry and Chemical Biology, Harvard University. After establishing her own lab in Academia Sinica, she attended the Physiology Course at Marine Biological Laboratory, Woods Hole, where she was captivated by the intricate inner workings of the cells. Her research now focuses on understanding how mammalian cells sense and respond to the third dimensionality and how utilize physical signals to perform biological functions. She was elected as a Young Affiliate of The World Academy of Sciences and received Taiwan Outstanding Young Female Scientist Award. 

Host: Arpita Upadhyaya

Seminars start at 4:00 pm, and refreshments will be served at 3:45 pm. 

This seminar will be held in room 3150 of the Physical Sciences Complex (Bldg #415).