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Shamreen-Iram-Dissertation.pdf (10.29 MB)

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Characterization and Control of Cellular Systems

Iram, Shamreen
http://orcid.org/0000-0002-4354-7407
http://rave.ohiolink.edu/etdc/view?acc_num=case1607450707990284

Abstract Details

2020, Doctor of Philosophy, Case Western Reserve University, Physics.
This dissertation explores analytical and numerical modeling to unpack, characterize and control the physics behind emergent patterns underlying various cellular level functions. We begin on the topic of characterizing cellular adhesion systems. In particular, we examine two physiologically relevant protein complexes using various different approaches. The first is the triphasic bond lifetime response of endothelial adhesion protein E selectin tethering on to mobile leukocytes in the blood stream. We model this adhesion-rupture process as an equivalent Kramers diffusive escape problem, and use theories of first passage times and network transition kinetics along with insight from force spectroscopic data and crystal structure data, to provide a detailed mechanistic basis for how such triphasic behavior arises. We then go on to the second of our adhesion systems arising in the inheritable blood disorder sickle cell disease (SCD). Diseased sickle red blood cells (sRBCs) from SCD patients show heightened adhesive interactions and altered morphology. Using whole channel images generated by a microfluidic assay which injects clinical SCD whole blood samples into sRBC-binding protein functionalized microchannels, we motivate a clinically relevant biophysical characterization. We then design a standardized and reproducible image analysis workflow, using a two part deep neural network architecture that works in tandem for automatic, fast and reliable segmentation and classification of adhered cell images. Continuing on the theme of translation applications, we make a brief stop to design an automated computer vision and deep learning assisted analyses protocol for an affordable, clinical standard, point-of-care paper-based electrophoresis test for blood Hb level quantification and anemia detection: the Hb Variant/Anemia (HbVA). The efficacy and performance of this new, integrated diagnostic approach is demonstrated against a globally accepted clinical standard control test of CBC. We then pivot to the second topical area of this dissertation: cellular level control. Specifically, we take up the problem of controlling the pace and direction of evolutionary trajectories for a mixed-variant cell colony evolving under drug application. To achieve this we use ideas originally developed in a very different context – counterdiabatic driving to control the behavior of quantum systems. Implementing this idea for the first time in a biological context, we show how a set of external control parameters can guide the probability distribution of genotypes in a population along a specified path and time interval.
Michael Hinczewski (Committee Chair)
Lydia Kisley (Committee Member)
Harsh Mathur (Committee Member)
Jacob Scott (Committee Member)
183 p.
Biophysics

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Citations

  • Iram, S. (2020). Characterization and Control of Cellular Systems [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1607450707990284

    APA Style (7th edition)

  • Iram, Shamreen. Characterization and Control of Cellular Systems. 2020. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1607450707990284.

    MLA Style (8th edition)

  • Iram, Shamreen. "Characterization and Control of Cellular Systems." Doctoral dissertation, Case Western Reserve University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1607450707990284

    Chicago Manual of Style (17th edition)

case1607450707990284
75
© 2020, some rights reserved.Creative Commons License Characterization and Control of Cellular Systems by Shamreen Iram is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.