Growth factor-induced cell migration using microfabricated devices
Item
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Title
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Growth factor-induced cell migration using microfabricated devices
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Identifier
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d_2009_2013:8c0c4be855ee:10185
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identifier
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10450
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Creator
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Kong, Qingjun,
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Contributor
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Maribel Vazquez
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Date
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2009
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biomedical engineering | Mechanical engineering | cell-cell contacts | cell migration | concentration gradient | growth factor | microfabrication | shear stress
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Abstract
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Over a quarter of a million people undergo surgical procedures to repair soft tissue such as ligaments and tendons in the United States each year. Multiple methodologies have been developed to enhance ligament healing in recent decades, as these tissues require years to fully recover mechanical properties. Growth factors have been widely applied to enhance soft tissue healing via cell proliferation and migration, as well as synthesis of extracellular matrix proteins.;Growth factor-induced cell migration is essential to tissue repair, as it is one of the first biological processes to initiate and regulate healing quality. Growth factors stimulate cells via receptor binding and intracellular signal transduction, which initiate multiple functions to achieve cell migration. Despite the volume of research in cell migration, it is still incompletely understood because of the complicated interactions between growth factors and their receptors, signal transduction pathways, and the effects of extracellular environment, including pH and temperature. Published findings have illustrated that growth factor gradients can direct cell migration, while increasing growth factor concentration primarily increases random cell motility. It has also been demonstrated that the spatial profiles and exposure time of growth factor gradients play important roles in cell migration. However, how these gradients impact cell migration remains incompletely understood.;In the past decade, researchers have developed various bioassays from macroscale to micro-scale that facilitate the study of growth factor-induced cell migration. The conventional bioassays designed in macro-scale, such as transwell assays, Zigmond chambers and scratch wound assays, lack precise measurements of growth factor concentration and gradient around individual cells over time. Hence, they cannot provide a platform with which to accurately analyze growth factor gradient-driven cell migration. Microfabrication, often integrated with imaging technology and computational modeling, has been widely used in biological studies to provide quantitative methodologies and platforms of single-cell analysis to investigate cell migration.;This work has utilized microfabrication to develop a novel microfluidic device, called the Bridged muLane System, to study cell migration in response to different spatiotemporal gradients of Epidermal Growth Factor (EGF). We have developed an optimal loading method to seed cells within the microenvironment, by examining how shear stress-induced cell-cell interconnections, cell-extracellular matrix interactions, and cell morphology affect cell migration. We observed that cell migration was EGF gradient-dependent, while EGF concentration also played an important role in regulating cell migration. Transient EGF gradients were found to be less effective on cell motility than steady-state gradients. The population of motile cells increased with EGF gradients, but decreased when higher EGF concentrations were used. Further, our experimental results suggest that EGF concentration and gradient are integrated to regulate cell migration.;Herein, we provide a platform with which to study cell migration with quantitative measurement of imposed growth factor gradients. This work can be applied to benefit a variety of cell migration investigations including tissue healing, immunological response, and cancer metastasis.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Engineering
