| Cell motion and behavior play a major role in both the healthy and diseased states of tissues. During cancer, development and wound repair cells multiply, change size and migrate. Cells in tissues move collectively, creating complex patterns or motion such as vortices and streams. As well, cells in confluent layers display multicellular, highly transient regions of increasing and decreasing density, requiring changes in cell size. While moving, cells generate tension via the contraction of their actomyosin cytoskeleton. This tension is balanced by the elasticity of the cell's environment: Through integrin binding sites on their basal surface and through cell-cell adhesions known as adherens junctions adherent cells pull on their neighbors and the surface to which they are attached. Moreover, cell tensions can potentially be balanced by internal compressive elements such as organelles and incompressible cytosolic fluid that fills the cell volume. For the volume changes observed in migrating cell layers to occur fluid would need to be taken in or expelled by cells. This link between cell size change, intercellular fluid motion, and cell forces has not been explored leaving a sizeable gap in our knowledge of collective cell behavior.;This dissertation investigates the interplay of cell volume regulation and cell force generation in the context of collective cellular behavior. We study collective motion in a model cell system: Madin Darby Canine Kidney (MDCK) epithelial monolayers. We investigate both single cell and multicellular motion within monolayers finding that groups of cells and individuals fluctuate in size with characteristic time scales and length scales. Finally, the preliminary results of indentation experiments show that fluid can be forced between groups of cells and that cells actively respond to externally applied pressures. |
