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Multimode Resonant Micromechanical Systems in Liquid for Biophysical Studies of Cells

Jia, Hao
http://orcid.org/0000-0002-1429-6995
http://rave.ohiolink.edu/etdc/view?acc_num=case1523324534404429

Abstract Details

2018, Doctor of Philosophy, Case Western Reserve University, EECS - Electrical Engineering.
Intercellular interactions (including adhesion, aggregation, separation, cluster migration, etc.) are among the most important aspects of cell biophysical studies, as they play an essential role in a variety of cellular behaviors and disease progressions, such as cancer metastasis. Recent progress in metastasis research has shown that circulating tumor cell (CTC) clusters foster an up to 50–100% increased metastatic potential compared with individual CTCs. Therefore, it is highly desirable to explore and advance fundamental knowledge and more importantly, enabling device technologies for quantitative understanding of the adhesive interaction and aggregation mechanisms in the metastatic cancer cell clusters. This dissertation tackles the biophysical challenges of probing cancer cell clustering behaviors through developing an innovative microdevice platform based on resonant multimode micromechanical systems. This chip-scale platform exploits the micro-Chaldni figure phenomena, and enables fast, versatile and non-invasive manipulation of cancer cells and their clusters, in vitro. By programming the formation and abrogation of cancer cell clusters via mechanical resonances, quantitative information about the metastatic cancer cell aggregation is obtained from the perspectives of intercellular adhesion and molecular binding. Employing this new platform, we have verified that metastatic breast cancer cell clustering is strongly correlated to the biomarker CD44 that is associated with cellular adhesion, and is mediated by its primary ligand, hyaluronic acid (HA). Eliminating CD44 expression destroys the CD44 based cellular adhesion mechanism; and inhibition of HA synthesis also weakens the adhesive interactions within the cancer cell clusters. This study addresses the knowledge gap and more importantly, the technology gap toward a better understanding of cancer cell clustering mechanisms and cancer metastasis. The microdevice technology developed and validated in this work may help pave the way for quantitative identification and screening of cancer biomarkers, which shall in turn help develop therapeutic strategies for destroying and preventing cancer cell aggregation and metastasis.
Philip Feng (Advisor)
Christian Zorman (Committee Member)
Steven Eppell (Committee Member)
Xin Yu (Committee Member)
Bo Li (Committee Member)
173 p.
Electrical Engineering

Recommended Citations

Citations

  • Jia, H. (2018). Multimode Resonant Micromechanical Systems in Liquid for Biophysical Studies of Cells [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1523324534404429

    APA Style (7th edition)

  • Jia, Hao. Multimode Resonant Micromechanical Systems in Liquid for Biophysical Studies of Cells. 2018. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1523324534404429.

    MLA Style (8th edition)

  • Jia, Hao. "Multimode Resonant Micromechanical Systems in Liquid for Biophysical Studies of Cells." Doctoral dissertation, Case Western Reserve University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1523324534404429

    Chicago Manual of Style (17th edition)

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© 2018, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.