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Microfluidic platforms for investigating cell migration

Posted on:2009-07-04Degree:Ph.DType:Dissertation
University:University of Illinois at Urbana-ChampaignCandidate:Silvestre, JonathanFull Text:PDF
GTID:1444390002991617Subject:Engineering
Abstract/Summary:
Cells respond to soluble or surface-bound chemical stimuli and migrate towards targeted areas in processes known as chemotaxis or haptotaxis. Integral to cell migration are the cell-surface and cell-cell adhesion molecules integrins and cadherins, respectively. Integrins mediate adhesion to and migration on extracellular matrix proteins, while cadherins are responsible for cell-cell adhesion and cell recognition. However, the assays used to investigate cell migration are limited in that they have uncontrollable cellular microenvironments. Therefore, quantitative measurements of the impact of integrin and/or cadherin ligation on cell migration are not attainable.;In this study, microfluidic platforms are fabricated to engineer microenvironments to investigate cell migration. The effects of the surface density and concentration profiles of extracellular matrix proteins on the migration of rat intestinal IEC-6 cells are quantified. This study investigated both the impact of the steepness and local concentrations on the directedness of cell migration. These investigations show that the cell directedness decreased at higher laminin mass coverage and increased at lower laminin densities. Cells migrated up the gradient, independent of the steepness of the gradients used in this study.;Furthermore, these studies quantified the relative effects of E-cadherin expression and adhesive ligation on the migration velocities of mammary breast tumor cells. Micropatterned proteins were used to titrate the relative effects of E-cadherin and Fibronectin on the migration velocities of the metastatic mammary epithelial tumor cells MDA-MB-231. These investigations show that increased E-cadherin expression reduces cell motility by both adhesion-dependent and adhesion-independent mechanisms. By controlling both the substratum composition and E-cadherin expression we defined conditions that favor either the adhesion-independent or the adhesion-dependent mechanism of motility suppression.
Keywords/Search Tags:Cell, E-cadherin expression
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