UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.
More information is available at Theses and Dissertations at University of Maryland Libraries.
Browse
2 results
Search Results
Item ESOTAXIS: IDENTIFYING THE FACTORS THAT INFLUENCE NANOTOPOGRAPHIC GUIDANCE OF THE DYNAMICS AND ORGANIZATION OF THE ACTIN CYTOSKELETON AND OTHER MOLECULES INVOLVED IN DIRECTED CELL MIGRATION(2024) Hourwitz, Matt; Fourkas, John T.; Losert, Wolfgang; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Directed migration is a crucial capability of cells in developmental and immunological processes. Defects in cell migration can lead to negative health outcomes. Cell motion depends on the organization and dynamics of internal components, especially the actin cytoskeleton, and the extracellular environment. Microscale and nanoscale topographical cues, with at least one dimension that is much smaller than most cells, can bias cell motion over long distances, due to the guidance of the organization and dynamics of the cytoskeleton and other molecules and assemblies within the cell. In this work, I describe a technique to reproduce patterned nanotopographic substrates for use in the study of esotaxis, the guided organization and dynamics of the actin cytoskeleton and other cellular components in response to nanotopographic cues. The guidance of actin drives directed cell motion along a pattern with dimensions much smaller than the cell. The dimensions of the nanotopography determine the extent to which cellular components are guided. Differences in the physical properties of the plasma membrane and the actin cytoskeleton among cell lines will influence the extent of guidance by nanotopography. Asymmetric patterns can accentuate the distinctions in esotactic responses among cell lines and drive contact guidance in different directions. The cytoskeletal response to nanotopography is a local phenomenon. A cell in contact with multiple nanotopographic cues simultaneously will show distinct organization of actin in the different regions of the cell. The importance of local actin dynamics requires an analysis method, optical flow, that can identify and track the distinct cytoskeletal motions in different parts of the cell. The formation of adhesions attached to the extracellular matrix is a characteristic of the migratory behavior of many types of cells and these adhesions are credited with allowing the cell to sense and interact with the underlying substrate. Actin can sense nanotopographic cues without the widespread availability of adhesive ligands. Although adhesion to the substrate strongly increases the extent of cell spreading and migration on nanoridges, epithelial cells can align with and migrate along nanotopography even with a dearth of adhesive cues. Therefore, actin is a supreme sensor of nanotopography that can drive directed cell migration.Item Directed Cell Migration: From Single Cells to Collectively Moving Cell Groups(2014) Guven, Can; Losert, Wolfgang; Ott, Edward; Physics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)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 individual and collective cell migration. At subcellular scale, the migration of cells can be guided via the interaction of the cell cytoskeleton with the surrounding nanotopographic 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 propagation speed and direction were obtained from experimental observations of cell migration on nanotopographic surfaces as a function of the spacing between adjacent features (varying between 0.8 and 5 microns). I show that actin polymerization is preferentially localized to nanoscale features for a range of spacings. Additionally, the velocity of actin polymerization waves moving parallel to the direction of nanoridges depends on the nanoridge spacing. A model of actin polymerization dynamics in which nanoridges modify the distribution of the nucleation promoting factors captures these key observations. For individual cells, the question is how the intracellular processes result in directed migration of cells. I introduce a coarse-grained model for cell migration to connect contact guidance to intrinsic cellular oscillations. The guidance of collective cell migration can be dictated via intercellular communication, which is facilitated by biochemical signals. I present a coarse-grained stochastic model for the influence of signal relay on the collective behavior of migrating Dictyostelium discoideum cells. In the experiment cells display a range of collective migration patterns including uncorrelated motion, formation of partially localized streams, and clumping, depending on the type of cell and the strength of the external concentration gradient of the signaling molecule cyclic adenosine monophosphate (cAMP). The collective migration model shows that the pattern of migration can be quantitatively described by considering the competition of two processes, the secretion of cAMP by the cells and the degradation of cAMP in the gradient chamber. With degradation, the model secreting cells form streams and efficiently traverse the gradient, but without degradation the model secreting cells form clumps without streaming. This observation indicates that streaming requires not only signal relay but also degradation of the signal. In addition, I show how this model can be extended to other eukaryotic systems that exhibit more complex cell-cell communication, in which the impact on collective migration is more subtle.