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In partial fulfillment of the requirements for the degree of
Doctor of Philosophy in Quantitative Biosciences
in the School of Physics
Shlomi Cohen
Defends his thesis:
The Biomechanical Role of Hyaluronan in Cell Adhesion and Migration
Monday, April 25, 2022
2:00pm Eastern Time
Petit Institute for Bioengineering and Biosciences (IBB)
Suddath Seminar Room #1128
Open to the Community
Dr. Jennifer Curtis
School of Physics
Georgia Institute of Technology
Dr. Shuyi Nie
School of Biological Sciences
Georgia Institute of Technology
Committee Members:
Dr. Andres Garcia
School of Mechanical Engineering
Georgia Institute of Technology
Dr. Khalid Salaita
Department of Chemistry
Emory University
Dr. Denis Tsygankov
School of Biomedical Engineering
Georgia Institute of Technology / Emory University
Abstract:
Cell adhesion and migration are essential to fundamental processes throughout the lifespan of multicellular organisms, including in embryonic development, tissue maintenance, and disease. Over the past several decades, researchers have established a deep molecular understanding of the mechanisms governing the attachment of cells to the extracellular matrix (ECM) through assemblies of adhesion proteins at the cell-ECM interface. However, sizable sugars and glycoproteins residing at the very same cell-ECM interface may also play an important yet unrecognized mechanical role in the regulation of cell adhesion and migration. Hyaluronan (HA), a giant sugar synthesized on the cell membrane by the HA synthase family is often confined at the cell-ECM interface as part of the membrane-bound HA-rich glycocalyx or embedded into macromolecular structures in the ECM. We hypothesized that confined HA at the cell-ECM interface is compressed, and the consequent repulsion may counteract adhesive forces to decrease the effective cell adhesion strength, and thereby modulate cell migration speed. We explored the potential biomechanical role of HA in vitro, ex vivo and in vivo, by manipulating cells to change the levels of interfacial HA and by quantifying the resulting cell morphology, adhesion, and migration responses. We then compared our results with polymer physics-based theoretical predictions and integrated them into experiment-driven models that predicted the repulsion force by compressed HA at the interface as well as HA-induced membrane configurations at the dorsal and ventral sides of the cell. Taken together, our results suggest another layer of regulation by HA exists in the molecular mechanisms governing cell adhesion and migration and they emphasize the hidden mechanical role sugars may play in other biological processes.
