Characterizing eukaryotic single cell motility via bimodal analysis

Abstract

Bimodal analysis, a cellular-scale approach to studying eukaryotic single cell migration by performing a model-based analysis of single cell video-microscopy data, is described. The bimodal framework that is a generalization of the run-and-tumble motion of bacteria segregates the cellular trajectories into two types of alternating modes, namely, the "directional-mode" (the more persistent mode, analogous to the bacterial run phase) and the "re-orientation-mode" (the less persistent mode, analogous to the bacterial tumble phase). The dissertation research reported here has three main aspects. The first is the measurement of epithelial single cell migration by video-microscopy, which is then characterized using a simple model-based tool, bimodal analysis, developed as part of this dissertation research. The second aspect is to model mammary epithelial single cell migration by means of a cellular dynamics simulation methodology and using a bimodal correlated random walk (BCRW) model. The BCRW model was developed to elucidate the search strategy of single epithelial cells from multi-cellular organisms. The third aspect deals with application of bimodal analysis tool to eclectic eukaryotic cell types (Dictyostelium, neutrophils, fibrosarcoma, prostate cancer in addition to mammary epithelial cells) in different motility assays/treatments to provide a common framework for studying eukaryotic single cell motility. In addition, a simple experimental setup for creating a temporal gradient of chemo-attractant for epithelial cells is described and the possibility of temporal gradient sensing by epithelial cells is studied.