Dynamic behaviors of in vitro pathophysiological models

Abstract

This dissertation elucidates the underlying mechanisms of various pathophysiological phenomena, bringing a physical perspective into cell analysis. To do so, we started with establishing in vitro models replicating the in vivo microenvironments, and parameters describing cellular migration and deformations were extracted from the models primarily using live-cell imaging. In this way, we report the followings in each of the four chapters: First, we explicate the mechanisms of lipid droplet secretion during adipocyte dedifferentiation and report the phenomena of lipid exchange between adipocytes. Second, we reveal that ovarian cancer cells exposed to substrates of different stiffnesses acquire different characteristics and retain their mechanical memory over multi-passages and culture conditions in an in vitro model that simulates the peritoneal metastatic process. Third, we find that the spheroid models of breast cancer exhibit different levels of collectiveness during invasion depending on the protocols chosen for the spheroid generation. Finally, we establish spheroid models of glioblastoma and investigated their multimodal invasion mechanisms. The above results suggest that the physical indicators quantifying the physical aspects of cells can be as powerful as the traditional cell analysis based on the expression level of genes or proteins in the study of various pathophysiological phenomena.