Date of Award
Doctor of Philosophy (PhD)
Mechanical & Aerospace Engineering
Mechanical communication of adherent cells with their micro-environment is mediated by cytoskeletal and adhesion proteins. These mechanical links aid tissues in maintaining their coherence in the context of the surrounding extra cellular matrix (ECM). Epithelial tissues exert force on the ECM through integrin-based junctions and maintain their coherency through E-cadherin-based cell-cell junctions while dynamically undergoing collective migration. Such a complex network of communication involving the cell cytoskeleton and adhesion proteins modulates the tissue's response to external cues. Two distinct forms of such external stimuli are those of electrical and mechanical origin.
Epithelial tissues quickly respond to physiologically relevant electric fields by moving toward one pole of the electric field. By pharmacological modulation of the actin cytoskeleton, we showed that the basic mechanism by which epithelial monolayers migrate is not altered by the application of external direct current (DC) electric filed despite their directionality being biased toward the cathode. It was shown that the DC electric field controls monolayer migration by affecting cell polarity rather than the speed of cell migration.
Epithelial islands respond to external mechanical signals by altering the traction force exerted on the substrate. Here, Fourier transform traction cytometry (FTTC) showed that the traction force, strain energy and sheet tension of micropatterned eipthelial islands increase upon the application of 10% uniaxial substrate stretch and continues to temporally increase. Interestingly, the sheet tension at the island mid-line parallel to the stretch direction reached levels similar to the sheet tension of the mid-line perpendicular to the stretch direction over time, indicating the island's tendency to homogenize its internal stress. Here, a modified protocol was used to measure the elastic properties of the soft silicon substrate required for FTTC. The validity of FTTC in quantification of the wall shear stress of small-scale flow-channels over a wide range of steady flow rates was also demonstrated.
"Epithelial Sheet Response to External Stimuli"
(2018). Doctor of Philosophy (PhD), dissertation, Mechanical & Aerospace Engineering, Old Dominion University, DOI: 10.25777/nz15-zg57