UC San Diego

Cell migration is the movement of a single cell or group of cells, usually in response to various environmental cues. It is crucial in many biological processes, including morphogenesis, immune response and metastasis of cancer cells. This dissertation studies eukaryotic cell migration from single cell level to collective behavior using both experiments and theoretical models. In Chapter 2, we study single cell migration of the social amoeba Dictyostelium discoideum and investigate the effect of background chemoattractant concentration on cellular memory in eukaryotic chemotaxis. Our results suggest that aggregation of Dictyostelium cells can be facilitated by a rising level of chemoattractant during its developmental program. In Chapter 3, we study the collective behavior of the social amoeba Dictyostelium discoideum during its multicellular mound stage. We find tight correlation between the traction force, signaling activity and cell velocity in the mound, all showing oscillations in their magnitude with the same period. With our mathematical model and perturbation experiments, we show that collective cell motion is crucial in setting up a persistent signaling vortex state within the mound. In Chapter 4, we study the collective behavior of breast cancer cells (MDA-MB-231) and liver cancer cells (SK-HEP-1) during their proliferation in dense extracellular matrices (ECMs). We find the formation of two distinct morphologies and migration modes, namely rotational spheroids and invasive networks. Our experimental and numerical results show that the localization of matrix-degrading enzymes is a key factor in distinguishing formation of the distinct structures and migration modes.