ABSTRACT Title of dissertation: DIRECTED CELL MIGRATION: FROM SINGLE CELLS TO COLLECTIVELY MOVING

Unlike molecules, which are driven thermally by Brownian motion, eukaryotic cells move in a particular direction to accomplish designated tasks that are involved in diverse biological processes such as organ development and tumor progression. In this dissertation, I present experiments, analysis, and modeling of directed in-dividual and collective cell migration. At subcellular scale, the migration of cells can be guided via the interaction of the cell cytoskeleton with the surrounding nan-otopographic elements. I show that mechanical waves of actin polymerization are involved in this guidance–known as contact guidance–as dynamic sensors of surface nanotopography. The dynamics of guided actin waves were measured to build and test predictive models of contact guidance. The distributions of actin-wave prop-agation speed and direction were obtained from experimental observations of cell migration on nanotopographic surfaces as a function of the spacing between adja-cent features (varying between 0.8 and 5 microns). I show that actin polymerization is preferentially localized to nanoscale features for a range of spacings. Addition-ally, the velocity of actin polymerization waves moving parallel to the direction o