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PhD Dissertation (Yunus Alapan).pdf (7.02 MB)

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MICROFABRICATED SYSTEMS INTEGRATED WITH BIOMOLECULAR PROBES FOR CELL MECHANICS

Alapan, Yunus
http://orcid.org/0000-0003-3064-7342
http://rave.ohiolink.edu/etdc/view?acc_num=case1466014738

Abstract Details

2016, Doctor of Philosophy, Case Western Reserve University, EMC - Mechanical Engineering.
Cell mechanics is a multidisciplinary field bridging cell biology with mechanics, and micro/nanotechnology, which synergize for better understanding of the complex nature of cells in their native microenvironment. Engineered microsystems integrated with biomolecular probes have remarkably robust compatibility with cells in terms of function, size, and physical properties. These new technologies have been rapidly advancing the cell mechanics field, such as in evaluation of mechanical alterations of red blood cells (RBCs) in sickle cell disease (SCD) and mechanical behavior of cells in directional three-dimensional (3D) microenvironments. Decreased deformability and increased adhesion of RBCs to vascular endothelium is at the root of vaso-occlusion, which is the clinical hallmark of SCD and can result in pain crisis, wide-spread organ damage, and early mortality. However, these factors have been studied in isolation due to significant technological barriers faced in directly analyzing blood samples from diverse clinical phenotypes. In this work, a microfluidic device (SCD Biochip) functionalized with endothelium associated biomolecular probes, that allows simultaneous interrogation of RBC properties in physiological flow conditions at a single cell level, is developed. With this method, deformability and adhesion strength of healthy hemoglobin (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs using whole blood samples from twelve subjects are studied. Heterogeneity of HbS-containing RBCs in terms of adhesion and deformability in flow is reported. Moreover, with the SCD Biochip, blood samples from over hundred subjects are analyzed and associations between the measured RBC adhesion to endothelium associated proteins and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count are shown. Furthermore, it is critical to mimic physical properties of the native 3D cell environment to achieve aligned and elongated cellular phenotype for controlled and hierarchical study of cell behavior. A microfabricated pillar substrate is developed to confine, align, and elongate cells, allowing decoupled analysis of stiffness and directionality in 3D. Mesenchymal stem cells and cardiomyocytes are successfully confined in a 3D environment with precisely tunable stiffness anisotropy. It is discovered that anisotropically stiff micropillar substrates provide cellular confinement in 3D, aligning cells in the stiffer direction with extraordinary elongation.
Umut Gurkan (Committee Chair)
Ozan Akkus (Committee Member)
Jane Little (Committee Member)
Joseph Mansour (Committee Member)
161 p.
Biomechanics; Biomedical Engineering; Mechanical Engineering

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Citations

  • Alapan, Y. (2016). MICROFABRICATED SYSTEMS INTEGRATED WITH BIOMOLECULAR PROBES FOR CELL MECHANICS [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1466014738

    APA Style (7th edition)

  • Alapan, Yunus. MICROFABRICATED SYSTEMS INTEGRATED WITH BIOMOLECULAR PROBES FOR CELL MECHANICS. 2016. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1466014738.

    MLA Style (8th edition)

  • Alapan, Yunus. "MICROFABRICATED SYSTEMS INTEGRATED WITH BIOMOLECULAR PROBES FOR CELL MECHANICS." Doctoral dissertation, Case Western Reserve University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1466014738

    Chicago Manual of Style (17th edition)

case1466014738
532
© 2016, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.