Biomarkers are biological characteristics that can be observed or measured during disease conditions, and compared to the healthy state. Biomarkers have been used in medical history to study disease progression, to develop drugs, or to predict drug efficacy. However, in complex diseases such as in cancer, biomarkers vary tremendously among patients and disease stages. Cell surface receptors, proteins that are located at the cell surface and deliver external signals into the cell, are a significant group of easily-detectable biomarkers. Along with the detection of particular biomarkers related to a disease, extensive characterization of expression patterns is necessary to optimize their application. Therefore, we designed a technique to imprint or capture the expression pattern of these receptors on silver nanoparticles. We incorporated branched molecules that can simultaneously bind to the target receptors and the nanoparticle surface. To develop the technique, we used melanocortin receptor 1 (MC1R), a receptor present at high levels on the surface of melanoma cells, as a test system. We determined optimum binding of this molecule in an established melanoma cell line, WM-266-4. We also synthesized a labeled molecule that was used to estimate the number of MC1R proteins on these cells. These studies indicate that this might be a promising approach for developing sensitive and cost-effective tools to characterize cell surface receptors in studying complex diseases and cell mechanisms. / MS / Biomarkers are biological characteristics that can be observed or measured during disease conditions, and compared to the healthy state (e.g. grades of fever during infection). Biomarkers have been used in medical history to study disease progression, to develop drugs, or to predict drug efficacy. However, in complex diseases such as in cancer, biomarkers vary tremendously among patients and disease stages. Cell surface receptors, proteins that are located at the cell surface and deliver external signals into the cell, are a significant group of easily-detectable biomarkers. Along with the detection of particular biomarkers related to a disease, extensive characterization of expression patterns is necessary to optimize their application. Therefore, we designed a technique to imprint or capture the expression pattern of these receptors on silver nanoparticles. We incorporated branched molecules that can simultaneously bind to the target receptors and the nanoparticle surface. To develop the technique, we used melanocortin receptor 1 (MC1R), a receptor present at high levels on the surface of melanoma cells, as a test system. We determined optimum binding of this molecule in an established melanoma cell line, WM-266-4. We also synthesized a labeled molecule that was used to estimate the number of MC1R proteins on these cells. These studies indicate that this might be a promising approach for developing sensitive and cost-effective tools to characterize cell surface receptors in studying complex diseases and cell mechanisms.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/98406 |
| Date | 22 January 2019 |
| Creators | Ahmed, Sadia |
| Contributors | Biological Sciences, Winkel, Brenda S. J., Lazar, Iuliana M., Rodriguez Corrales, Jose Angel, Kojima, Shihoko |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf, application/x-zip-compressed |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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